Particles containing agricultural active ingredients

ABSTRACT

One or more agricultural active ingredients (such as fungicides or insecticides) are entrapped in polymeric matrixes to form particles having a diameter in the range from about 0.2 to about 200 microns. The particles are applied to soil, to seeds, or to plants and release the active ingredient(s) at a rate sufficiently low to avoid phytoxicity but at a rate sufficiently high to provide effective amounts of the active ingredient(s), preferably throughout the growing period of the plant.

RELATED APPLICATION

This application is a divisional of co-pending U.S. patent applicationSer. No. 09/326,014, filed Jun. 4, 1999, which is a continuation-in-partof U.S. patent application Ser. No. 09/104,565, filed Jun. 25, 1998(abandoned), which was a non-provisional of U.S. Provisional ApplicationNo. 60/051,285 filed Jun. 30, 1997, each of which is incorporated hereinby reference.

BACKGROUND OF THE INVENTION

This invention relates to compositions and methods for controlledrelease of agricultural chemicals.

An agricultural chemical, such as a biocide, a chemical hybridizingagent, or a plant growth regulator is applied to a plant, to a seed, orto soil at the beginning of a growing season and must maintain theireffectiveness throughout the growing season, which can last for severalmonths. However, the agricultural chemical may be degraded by chemicalor biological processes and removed by wind or water from the site ofapplication. As a result, it is necessary to apply high rates of theagricultural chemical to maintain the desired effect over time or toapply the chemical repeatedly during the growing season. However, highrates of certain agricultural chemicals can be phytotoxic to a plantwhich is sought to be protected (“agronomic plant”) from the disease orpest which the agricultural chemical is meant to control. For example,many fungicides, such as triazole fungicides, can be phytotoxic to theagronomic plant when applied in amounts that are necessary to provideagronomically adequate disease control.

Numerous triazole fungicides have been developed and commercialized. Thetriazole fungicides are generally characterized as having a1H-1,2,4-triazole group. Some individual representative triazolefungicides are listed in the table below. CAS Registry TriazoleFungicide Number bitertanol 70585-36-3 bromuconazole 116255-48-2cyproconazole 94361-06-5 difenoconazole 119446-68-3 epoxiconazole106325-08-0 fenbuconazole 114369-43-6 fluquinconazole 136426-54-5flusilazole 85509-19-9 flutriafol 76674-21-0 hexaconazole 79983-71-4imibenconazole 86598-92-7 metconazole 125116-23-6 myclobutanil88671-89-0 penconazole 66246-88-6 propiconazole 60207-90-1 tebuconazole107534-96-3 tetraconazole 112281-77-3 triadimefon 43121-43-3 triadimenol55219-65-3 triticonazole 131983-72-7

Under certain conditions, a triazole fungicide frequently is phytotoxicto the very plant species the fungicide is meant to protect fromdisease. For example triadimefon can be phytotoxic to ornamental plants(The Pesticide Manual, Eleventh Edition, C. D. S. Tomlin, ed., TheBritish Crop Protection Council, Farnham, Surrey, U.K., 1997, p. 1217);metconazole can cause stunting and yellowing of plants (Id., p. 804);hexaconazole can cause damage to McIntosh apples (Id., p. 675);difenoconazole can cause chlorosis in wheat (Id., p. 390); andbitertanol can cause damage to fruit crops (Id., p. 132).

Controlled release of a pesticide has occasionally been used as a methodof controlling phytotoxicity of the pesticide to the beneficial plantspecies. Patents and published patent applications disclosing variouscontrolled-release formulations include each of the following individualdisclosures.

U.S. Pat. No. 4,172,119.

U.S. Pat. No. 4,915,947.

U.S. Pat. No. 5,225,278.

U.S. Pat. No. 5,277,979.

U.S. Pat. No. 5,725,869.

European Patent Publication No. 0 004 758-A2.

European Patent Publication No. 0 018 119-A1.

European Patent Publication No. 0 763 510-A1.

PCT Patent Application No. WO 88/08300.

SUMMARY OF THE INVENTION

Thus, there is a continuing need for controlled-release formulations bywhich an agricultural chemical can be delivered to a plant over theentire growing season at a concentration or rate which is agronomicallyeffective, while reducing plant phytotoxicity relative to currentcommercially used practices. There is especially a need for acontrolled-release formulation of a fungicide such as a triazolefungicide which can provide effective fungicidal control over a periodof time without causing unacceptable phytotoxic damage to anagriculturally beneficial plant to which the formulation is applied.

Preferably, such formulations would include an amount of an activeingredient that is close to the minimum amount needed to obtain thedesired effect in order to reduce environmental impacts and to reducecosts.

Among the many embodiments of the present invention may be noted acontrolled-release formulation which comprises a particle in which oneor more agricultural active ingredients are dispersed or distributed ina polymeric matrix. Such controlled-release formulations are safe whenapplied to seeds or to plants even though they contain levels of activeingredients that would be phytotoxic if applied to the seeds or plantsin standard fast-release formulations. The particle of the presentinvention can release at least one active ingredient at biocidallybeneficial levels over a period during the germination and growth of anagriculturally beneficial plant (e.g., for at least two to twelve weeksor more) and therefore can reduce or eliminate the need for subsequentapplications of the agricultural chemical. The rate of release ofagricultural chemicals, and the period over which effective amounts ofsuch chemicals can be released, can be tailored as desired. Suchcontrolled-release compositions thus increase the period during which anagricultural chemical is effective, reduce the initial toxicity of thechemical to seeds or crop plants, expand the range of compounds that canbe used for agricultural applications, and decrease the environmentalimpact of chemical treatment.

In one embodiment, the present invention presents a particle comprisinga triazole fungicide in a polymer matrix. Preferably, the triazolefungicide comprises a compound selected from the group consisting ofbitertanol, bromuconazole, cyproconazole, difenoconazole, epoxiconazole,fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole,imibenconazole, metconazole, myclobutanil, penconazole, propiconazole,tebuconazole, tetraconazole, triadimefon, triadimenol, andtriticonazole. The present invention further embodies a fungicidalcomposition comprising a particle comprising a triazole fungicide in apolymer matrix, and an agricultural adjuvant.

In another embodiment of the invention, controlled-release compositionsfor delivering an agricultural chemical to a plant comprise particleshaving an average diameter of about 0.1 microns to about 200 microns,the particles each comprising a polymer matrix and at least oneagricultural chemical distributed throughout the polymer matrix. Theparticles include about 1 to about 50% by weight of the agriculturalchemical and about 50% to about 99% by weight of the polymer matrix.

In a further embodiment, the present invention provides compositionsincluding suspensions of the particles in an aqueous medium, wettablepowders, wettable granules, dry granules, and seed coatings, forexample. According to at least some embodiments of the invention, theparticles adhere to a surface of a seed or plant.

A further embodiment of the present invention comprises compositionswhich include an amount of the agricultural chemical and which releasethe agricultural chemical at a rate such that the composition deliversan agriculturally active amount of the agricultural chemical to theplant for a period of at least about two weeks to about twelve weeks,preferably throughout the growth period of the plant.

In yet another embodiment of the invention, such compositions asdescribed in the present disclosure can be used in a method to reducethe phytotoxicity of the agricultural chemical by at least two-fold(i.e., at least a 50% reduction in phytotoxicity as compared toconventional fast-release formulations of the chemical). For example, inthe case of seed coating compositions according to the presentinvention, the composition can include an amount of the agriculturalchemical that would be substantially phytotoxic if applied to thesurface of the seed as a fast-release formulation of the agriculturalchemical. One embodiment of the present invention provides a method forthe treatment or prophylaxis of a fungal disease in a target plantwherein the method comprises contacting a plant cell, a plant tissue, ora seed with a particle wherein the particle comprises a triazolefungicide in a polymer matrix and wherein after the contacting, thehealth of the target plant is substantially similar to the health of acontrol plant which is substantially free of the fungal disease andwhich is free of contact with the triazole fungicide.

Another embodiment of the present invention provides a method for thetreatment or prophylaxis of a fungal disease in a target plant whereinthe method comprises contacting a plant cell, a plant tissue, or a seedwith a particle wherein the particle comprises a triazole fungicide in apolymer matrix and wherein after the contacting, the health of thetarget plant is intermediate between the health of a first control plantwhich is substantially free of the fungal disease and which is free ofcontact with the triazole fungicide, and the health of a second controlplant which is substantially free of the fungal disease and which iscontacted with the triazole fungicide in the absence of the polymermatrix. Commercially acceptable levels of disease control (e.g., fungalcontrol) frequently results from plants in which less than 100% of thedisease agent (e.g. a fungus) has been eradicated. For example, in somecircumstances and markets, a treatment providing 60-80% fungal diseasecontrol is considered commercially acceptable.

In a further embodiment of the invention, the agricultural chemicalcomprises a biocide (e.g., a triazole fungicide such as bitertanol,bromuconazole, cyproconazole, difenoconazole, epoxiconazole,fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole,imibenconazole, metconazole, myclobutanil, penconazole, propiconazole,tebuconazole, tetraconazole, triadimefon, triadimenol, ortriticonazole), a plant growth regulator, a chemical hybridizing agent,a plant nutrient, or combinations thereof.

In one embodiment, the polymer used in the compositions of the presentinvention is selected from the group consisting ofpoly(methylmethacrylate), poly(lactic acid), poly(lactic acid-glycolicacid) copolymers, cellulose acetate butyrate, poly(styrene),hydroxybutyric acid-hydroxyvaleric acid copolymers, styrene maleicanhydride copolymers, poly(methylvinyl ether-maleic acid),poly(caprolactone), poly(n-amylmethacrylate), wood rosin,polyanhydrides, polyorthoesters, poly(cyanoacrylates), poly(dioxanone),ethyl cellulose, ethyl vinyl acetate polymers, poly(ethylene glycol),poly(vinylpyrrolidone), acetylated mono-, di-, and trigylcerides,poly(phosphazene), chlorinated natural rubber, vinyl polymers, polyvinylchloride, hydroxyalkylcelluloses, polybutadiene, polyurethane,vinylidene chloride polymers, styrene-butadiene copolymers,styrene-acrylic copolymers, alkylvinylether polymers, cellulose acetatephthalates, ethyl vinyl pthalates, cellulose triacetate, polyanhydrides,polyglutamates, polyhydroxy butyrates, polyvinyl acetate, vinylacetate-ethylene copolymers, vinyl acetate-vinylpyrrolidone copolymers,acrylic polymers, alkyl acrylate polymers, aryl acrylate polymers, arylmethacrylate polymers, poly(caprolactams), epoxy resins, polyamine epoxyresins, polyamides, polyvinyl alcohol polymers, polyalkyd resins,phenolic resins, abietic acid resins, silicones, polyesters, andcopolymers and combinations thereof.

The present invention further embodies compositions which include adispersing agent, such as methyl cellulose, poly(vinyl alcohol),lecithin, and combinations thereof.

In another embodiment of the invention, seeds are provided that comprisesuch compositions, e.g., as seed coatings.

A further embodiment of the invention provides a method for deliveringan agricultural chemical to a plant wherein the method comprisesproviding to the plant a composition as discussed above, for example, byapplication of the composition to soil, application of the compositionto foliage of the plant, and coating a seed prior to germination of theseed to produce the plant. When applied to soil or foliage thecomposition can be applied, for example, in an amount such that about 1g to about 10 kg of the agricultural chemical is applied per hectare.When applied as a seed coating, the composition can be applied in anamount such that about 1 gram to about 500 grams of the agriculturalchemical is applied to 100 kg of seed.

In a further embodiment of the invention, methods are provided forproducing the compositions described above. Such methods include thesteps of: (a) dissolving at least one agricultural chemical (forexample, a triazole fungicide) and a polymer in a to form a hydrophobicsolution; (b) mixing the hydrophobic solution and an aqueous medium at ashear rate and for a time period sufficient to produce an emulsionhaving droplets of the hydrophobic solution dispersed in the aqueousmedium; and (c) evaporating the organic solvent from the emulsion toproduce a plurality of particles having an average diameter of about 0.2micron to about 200 microns and comprising said at least oneagricultural chemical distributed throughout a polymer matrix. Accordingto some embodiments of the invention, such methods include one or moreof the further steps of: dissolving a dispersing agent in an aqueoussolution to produce the hydrophilic solution; and suspending theparticles in an aqueous medium.

A preferred embodiment of the present invention provides a method ofproducing a particle wherein the particle comprises a triazole fungicidein a polymer matrix, and the method comprises providing a hydrophobicsolution comprising a triazole fungicide, a polymer, and a solvent;mixing the hydrophobic solution and an aqueous medium to produce adispersion of droplets of the hydrophobic solution in the aqueousmedium; and evaporating the solvent from the dispersion to produce aparticle comprising a triazole fungicide in a polymer matrix.

A further embodiment of the present invention provides a method ofproducing a particle wherein the particle comprises a triazole fungicidein a polymer matrix, the method comprising the steps of providing ahydrophobic solution comprising a triazole fungicide, a polymer, and asolvent; mixing the hydrophobic solution and an aqueous medium toproduce a dispersion of droplets of the hydrophobic solution in theaqueous medium; and evaporating the solvent from the dispersion toproduce a particle comprising a triazole fungicide in a polymer matrix.

The present invention also embodies a method for the treatment orprophylaxis of a fungal disease in a target plant wherein the methodcomprises contacting a plant cell, a plant tissue, or a seed with aparticle wherein the particle comprises a triazole fungicide in apolymer matrix.

Other aspects of the present invention will become apparent to thoseskilled in the art upon studying this disclosure and the accompanyingclaims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the effect of matrix particle formulations of Example 7 andAlto 005LS when used as seed treatments on wheat at various rates (gcyproconazole per 100 kg seed), expressed as the height of germinatingwheat at 11 days after planting (DAP) as a percent of the height ofuntreated controls.

FIG. 2 shows the effect of matrix particle formulations of Example 8 andAlto 005LS when used as seed treatments on wheat at various rates (gcyproconazole per 100 kg seed), expressed as the height of germinatingwheat at 10 DAP as a percent of the height of untreated controls.

FIG. 3 shows the effect of matrix particle formulations of Example 9 andAlto 005LS when used as seed treatments on wheat at various rates (gcyproconazole per 100 kg seed), expressed as the height of germinatingwheat at 10 DAP as a percent of the height of untreated controls.

FIG. 4 shows the effect of matrix particle formulations of Example 10and Alto 005LS when used as seed treatments on wheat at various rates (gcyproconazole per 100 kg seed), expressed as the height of germinatingwheat at 11 DAP as a percent of the height of untreated controls.

FIGS. 5 and 6 show the effect of a matrix particle formulation ofExample 11, Formulation 29, and Alto 005LS when used as a seed treatmenton wheat at various rates (g cyproconazole per 100 kg seed), expressedas the height of germinating wheat at 10 DAP (FIG. 5) or 9 DAP (FIG. 6)as a percent of the height of untreated controls.

FIG. 7 shows the effect of matrix particle formulations of Example 12,Formulation 29, Formulation 31, and Alto 005LS, when used as seedtreatments on wheat at various rates (g cyproconazole per 100 kg seed),expressed as the height of germinating wheat as a percent of the heightof untreated controls at 9 DAP.

FIG. 8 shows the effect of matrix particle formulations of Example 12,Formulation 31, Formulation 32, and Alto 005LS, when used as seedtreatments on wheat at various rates (g cyproconazole per 100 kg seed),expressed as the height of germinating wheat as a percent of the heightof untreated controls at 10 DAP.

FIG. 9 shows the effect of matrix particle formulations of Example 13,Formulation 33 and Formulation 34, and Alto 005LS, when used as seedtreatments on wheat at various rates (g cyproconazole per 100 kg seed),expressed as the height of germinating wheat as a percent of the heightof untreated controls at 10 DAP.

FIG. 10 shows the effect of a matrix particle formulation of Example 13,Formulation 35, and Alto 005LS, when used as seed treatments on wheat atvarious rates (g cyproconazole per 100 kg seed), expressed as the heightof germinating wheat as a percent of the height of untreated controls at10 DAP.

FIG. 11 shows the effect of matrix particle formulations of Example 14and Alto 005LS when used as seed treatments on wheat at various rates (gcyproconazole per 100 kg seed), expressed as the height of germinatingwheat as a percent of the height of untreated controls at 10 DAP.

FIG. 12 shows the effect of matrix particle formulations of Example 15and Alto 005LS when used as seed treatments on wheat at various rates (gcyproconazole per 100 kg seed), expressed as the height of germinatingwheat as a percent of the height of untreated controls at 10 DAP.

FIG. 13 shows the effect of matrix particle formulations of Example 16and Alto 005LS when used as seed treatments on wheat at various rates (gcyproconazole per 100 kg seed), expressed as the height of germinatingwheat as a percent of the height of untreated controls at 10 DAP.

FIG. 14 shows the effect of matrix particle formulations of Examples 17and 18, Formulation 43 and Formulation 44, respectively, and Raxil whenused as seed treatments on wheat at various rates (g tebuconazole per100 kg seed), expressed as the height of germinating wheat as a percentof the height of untreated controls at 11 DAP.

FIG. 15 shows the effect of matrix particle formulations of Examples 19and 20, Formulation 45 and Formulation 46, respectively, and Opus whenused as seed treatments on wheat at various rates (g epoxiconazole per100 kg seed), expressed as the height of germinating wheat as a percentof the height of untreated controls at 11 DAP.

FIG. 16 shows the effect of matrix particle formulations of Example 21at an application rate of 16 g cyproconazole per 100 kg seed and Alto005LS when used as seed treatments on wheat, expressed as the height ofgerminating wheat as a percent of the height of untreated controls at 8DAP.

FIG. 17 shows control of brown rust of wheat (second leaf) by seedcoatings comprising matrix particle Formulation 47, Formulation 15,Formulation 77 (each at 32 g cyproconazole per 100 kg seed), and Alto005LS (1 g cyproconazole per 100 kg seed). Plants were inoculated 20DAP. Disease severity in untreated controls was 61.3%.

DETAILED DESCRIPTION OF THE INVENTION

The following detailed description is provided to aid those skilled inthe art in practicing the present invention. Even so, this detaileddescription should not be construed to unduly limit the presentinvention as modifications and variations in the embodiments discussedherein can be made by those of ordinary skill in the art withoutdeparting from the spirit or scope of the present inventive discovery.

The contents of each of the references cited herein, including thecontents of the references cited within these primary references, areherein incorporated by reference in their entirety.

a. Definitions

The following definitions are provided in order to aid the reader inunderstanding the detailed description of the present invention:

“Agricultural chemical” or “active ingredient” means a chemical which isuseful in the control of a disease or a pest (including withoutlimitation a weed, an insect, a parasite, and a fungus) in agriculturalsettings.

The abbreviation “a.i.” means active ingredient.

“Phytotoxic” means injurious to vegetation.

“Agronomic plant” means a plant useful in agriculture and which issought to be protected from disease or pests.

“Agriculturally beneficial” means useful or productive in agriculture.

“Agricultural adjuvant” or “inert ingredient” means a material used inan agricultural formulation or composition to aid in the operation or toimprove the effectiveness of an agricultural chemical. The term includessuch materials as a wetting agent, a spreader, an emulsifier, adispersing agent, a foaming adjuvant, a foam suppressant, an antifoam, apenetrant, a corrective, a surfactant, a solvent, a solubilizer, abuffering agent, and a sticker.

The term “combination” is intended to embrace application of each agentin a sequential manner in a regimen that will provide beneficial effectsof the agricultural chemical combination, and is intended as well toembrace compositions or co-administration of these agents in which thepresence or application of these agents occurs in a substantiallysimultaneous manner, such as in a single spray mixture or treatmenthaving a fixed ratio of these active agents.

b. Compositions and Methods

The matrix particle formulations of this invention are useful inagriculture for a number of purposes, including, for example, thecontrol of seed-borne and soil-borne pathogens and pests, as well aspests affecting above-ground portions of plants (for example, stems,foliage, flowers, fruits), and underground portions (for example, roots,rhizomes, tubers) for the delivery of nutrients, chemical hybridizingagents and plant growth regulators, and the like. It will also beappreciated that such formulations have a number of non-agriculturaluses, such as in the delivery of pharmaceuticals to humans or to animalsfor therapeutic or prophylactic purposes; for the controlled release ofchemicals in water treatment or conditioning, aquaculture, etc.

Controlled-release formulations according to the present inventionsubstantially reduce the phytotoxicity of an agricultural chemical to aseed or a plant compared to a standard fast-release formulation of thechemical (i.e., one having a release rate that is substantially similarto that of the unformulated chemical). That is, such controlled-releaseformulations reduce the toxicity of, and correspondingly increase the“safety” of (or “safen”), the agricultural chemical. Therefore, for agiven level of phytotoxicity, more of the chemical can be applied to aseed or a plant in the form of a controlled-release formulationaccording to the present invention than in a standard fast-releaseformulation. Preferably, a controlled-release formulation according tothe present invention safens a particular chemical by at least two-fold(i.e., at least a 50% reduction in phytotoxicity as compared toconventional fast-release formulations of the chemical), more preferablyby at least five-fold (i.e., at least a 80% reduction in phytotoxicityas compared to conventional fast-release formulations of the chemical),yet more preferably by at least ten-fold (i.e., at least a 90% reductionin phytotoxicity as compared to conventional fast-release formulationsof the chemical), and most preferably by at least twenty-fold (i.e., atleast a 95% reduction in phytotoxicity as compared to conventionalfast-release formulations of the chemical). In fact, we have appliedgreater than one hundred times the amount of standard formulations ofcertain phytotoxic chemicals with only minimal injury to plants. Asshown in the Examples below, the safening of various agriculturalchemicals such as triazole fungicides permits their use as seedtreatments at levels that would otherwise prevent germination or stuntthe growth of plants that germinate from the seeds, making them moreeffective against various pathogens and pests.

Matrix particle. The term “matrix” is defined as a surrounding materialin which another material is entrapped, embedded, dissolved, dispersedor otherwise distributed. Particles of the present invention comprise amatrix that includes one or more polymers in which one or more activeingredients are entrapped, embedded, dissolved, dispersed, or otherwisedistributed. The particles may also include one or more inertingredients or additives, such as dispersants. The particles of thepresent invention differ from “microcapsules,” in which a polymericshell surrounds a liquid or solid core that contains an activeingredient. The core of the particle may be divided into a number ofseparate domains or multiple cores. In at least some embodiments of theparticles of the present invention, the final product appears infreeze-fracture electron micrographs as solid, generally sphericalparticles that appear solid throughout, indicating that the activeingredient(s) is distributed or dispersed within the-matrix material.The distribution may be at a molecular level or the distribution may beas finely divided pockets comprising a plurality of molecules of theactive ingredient. The distribution may be substantially uniformthroughout the matrix material or the distribution may exhibit aconcentration gradient through a cross-section of the matrix material.Therefore it is possible in at lease some embodiments that an activeingredient may be macromolecularly distributed in the matrix, i.e., thata plurality of particles of the active ingredient are dispersed in thematrix.

The agriculturally active ingredient can comprise about 1.0% to about50% by weight, preferably about 15% to about 50% by weight of theparticle of the present invention. The particle can comprise from about50 to about 99% by weight of matrix material. It is preferred that theparticle comprise from about 50% to about 90% by weight of the matrixmaterial. It is particularly economical if the particle comprises a highproportion of the active ingredient. If the proportion of matrixmaterial to entrapped active ingredient is too high, the rate of releaseof the entrapped material may decrease, thereby causing a decrease inthe biological efficacy of the treatment, and causing an increase in thecost of a biologically effective amount of the final product. If theproportion of the matrix component to the entrapped material componentis too small, the rate of release may be unacceptably high, leading tophytotoxicity and reducing the period of effectiveness of the activeingredient. As the concentration of the active ingredient increases inthe particle, the release rate will also generally increase.

The average matrix component concentration, as a percent of the totalweight of the matrix particle (combined weight of matrix, activeingredient and any other ingredients associated with the polymermatrix), can be estimated from the amount of ingredients in thecomposition used for preparing the particle.

The particle of the present invention preferably has an average particlesize in the range of about 0.2 microns to about 200 microns in diameter.Release rate of the active ingredient is generally inverselyproportional to the average particle size. Frequently plantphytotoxicity of the treatment comprising the particle of the presentinvention is inversely proportional to the average particle size.Smaller average particle sizes generally have a higher release rate andarea coverage of active ingredient, together with a higher activity andphytotoxicity of the active ingredient. Conversely, larger averageparticle sizes are associated with low area coverage and reducedphytotoxicity, but also lower activity and phytotoxicity. In addition,the small size of the particle of the present invention will permit theparticle to be taken up by a plant together with soil water and to betransported throughout the plant, effecting systemic delivery of activeingredient. The average particle size is preferably about 1 micron toabout 50 microns in diameter, more preferably about 3 to about 50microns. The size of the matrix particles is controlled during theprocess of entrapment by employing a mixing, stirring, or agitatingmeans (for example, a blender, a rotostator, a shaker, a vibrator, ahomogenizer, a mill, a microdropping syringe, or a sonicator at asuitable rate of speed to form droplets of the ingredients to beentrapped.

The particle size distribution of a batch of matrix particles of thepresent invention can be monomodal, bimodal, or polymodal. The differentmodalities can offer different advantages depending upon the desiredapplication. For example, a monomodal particle size distribution mayprovide a relatively uniform release rate of the active ingredient. Incontrast, a bimodal or a polymodal particle size distribution mayprovide more than one release rate of the active ingredient, therebyaffording an active ingredient release rate profile tailored to thespecific agricultural situation.

The particle size of the matrix particle of this invention is measuredby using a microscope with a calibrated reticle and visually estimatingthe average particle size. Alternatively, the size can be determined byelectronic means, for example by using a Coulter LS Counter or by laserlight scattering. Microscopic determination generally is within 5microns of the size measured by the Coulter Counter. From thedistribution of particle sizes, d₁₆, d₅₀ and d₈₄ values are determinedand plotted in a log probability plot. The d₁₆ value represents the size(diameter in microns) at which 16 weight percent of the capsules in thesample are equal to or larger than d₁₆, d₅₀ represents the size at which50 weight percent of the capsules are equal to or greater in diameterthan d₅₀, and d₈₄ represents the size at which 84 weight percent of theparticles are equal to or greater in diameter than d₈₄.

The particle of the present invention preferably adheres to the surfaceof a seed or a plant. Without being limited by theory, it is thoughtthat the particle becomes trapped in microhairs or in crevices on theseed or plant surface. Alternatively, the particle may adhere to asurface moiety of the plant, such as to the cuticle. Adhesion of theparticle to the seed or the plant can be enhanced or achieved by the useof conventional “sticking agents” (i.e., “stickers” or “tackifiers”) orother compounds that have been used for applying various coatings toseeds.

Particles can affect the mobility of an active ingredient in soil, sincethe binding or retention of the particle to soil can be substantiallydifferent than the binding of the active ingredient itself. As a result,depending on the matrix material selected, the composition according tothe present invention can increase the effectiveness of an agriculturalchemical that would be rendered less effective due to tight binding ofthe agricultural chemical to soil.

Also encompassed by the present invention is a particle comprising anagricultural chemical (such as a triazole fungicide) in a polymer matrixwherein the particle further comprises an encapsulation shell or coatingon the surface of the particle. Such shell or coating can be applied tothe particle by conventional methods and can provide further control ofrelease of active ingredients, add additional active or otheringredients, or confer desirable properties to the resulting product.

Polymer. The term “polymer” or “polymeric material” as used in thisinvention is taken to mean either a single polymer or a combination ofdifferent polymers or a copolymer. The particle comprises from about 50%to about 99% by weight of the polymeric material, preferably from about50% to about 90% by weight.

A matrix material is selected so that the rate of release of the activeingredient provides an “agriculturally effective amount” of the activeingredient, i.e., an amount of the active ingredient that is effectiveto achieve a desired level crop protection or other-desired agriculturalactivity characteristically associated with the agricultural chemical.Thus, for a biocide, an agriculturally effective amount is an amountthat is sufficient to provide commercially acceptable control of apathogen or pest; for a plant growth regulator, an amount that issufficient to substantially alter the growth or development of the plantin a manner characteristic of the plant growth regulator; for anutrient, an amount that is sufficient to provide at least the minimumamount of the nutrient required for normal plant growth and development.Preferably, the active ingredient is released at a rate that does notcause substantial phytotoxicity, i.e., does not reduce the growth orvigor of the plant to commercially unacceptable levels or produce othertypes of unacceptable damage to the plant. Preferably, the activeingredient is released at beneficial levels throughout the period ofgermination, emergence, later developmental stages of the crop or plant,or throughout the entire growth period of the plant. The activeingredient may be released by diffusion from the matrix or by thedegradation or dissolution of the matrix in the plant, soil or foliarenvironment. In addition, the polymer and breakdown products thereof, ifany, should not substantially interfere with the effectiveness of theactive ingredient (or other components, such as the dispersing agent) orbe substantially phytotoxic to the seed, seedling or plant.

Examples of suitable polymers for the practice of this invention includebut are not limited to the following non-exhaustive list of polymers(and copolymers and mixtures thereof):

-   -   poly(methylmethacrylate)    -   poly(lactic acid) (Chronopols 50, 95, and 100) and copolymers        such        -   as poly(lactic acid-glycolic acid) copolymers (Lactel            BP-400) and combinations with polystyrene, for example    -   cellulose acetate butyrate    -   poly(styrene)    -   hydroxybutyric acid-hydroxyvaleric acid copolymers (Biopol        D400G)    -   styrene maleic anhydride copolymers (SMA 1440 A Resin, Sartomer        Co.)    -   poly(methylvinyl ether-maleic acid)    -   poly(caprolactone)    -   poly(n-amylmethacrylate)    -   wood rosin    -   polyanhydrides, e.g., poly(sebacic anhydride), poly(valeric        anhydride), poly(trimethylene carbonate), etc., and copolymers        such as poly(carboxyphenoxypropane-sebacic acid), poly(fumaric        acid-sebacic acid), etc.    -   Polyorthoesters    -   poly(cyanoacrylates)    -   poly(dioxanone)    -   ethyl cellulose    -   ethyl vinyl acetate polymers and copolymers    -   poly(ethylene glycol)    -   poly(vinylpyrrolidone)    -   acetylated mono-, di-, and triglycerides    -   poly(phosphazene)    -   chlorinated natural rubber    -   vinyl polymers and copolymers    -   polyvinyl chloride    -   Hydroxyalkylcelluloses    -   Polybutadiene    -   Polyurethane    -   vinylidene chloride polymers and copolymers    -   styrene-butadiene copolymers    -   styrene-acrylic copolymers    -   vinyl acetate polymers and copolymers (e.g., vinyl        acetate-ethylene copolymers (Vinumuls) and vinyl        acetate-vinylpyrrolidone copolymers    -   alkylvinylether polymers and copolymers    -   cellulose acetate phthalates    -   ethyl vinyl pthalates    -   cellulose triacetate    -   Polyanhydrides    -   Polyglutamates    -   polyhydroxy butyrates    -   acrylic polymers (Rhoplexes)    -   alkyl acrylate polymers and copolymers    -   aryl acrylate polymers and copolymers    -   aryl methacrylate polymers and copolymers    -   poly(caprolactams) (i.e., the nitrogen-containing counterparts        to caprolactones)    -   epoxy/polyamine epoxy/polyamides    -   polyvinyl alcohol polymers and copolymers    -   silicones    -   polyesters (for oil-based approaches, including alkyds)    -   phenolics (polymers and copolymers with drying oils)

Preferred polymers include:

-   -   poly(methylmethacrylate)    -   poly(lactic acid) (Chronopols 50, 95, or 100) and combinations        with polystyrene    -   poly(lactic acid-glycolic acid) copolymers (Lactel BP400)    -   cellulose acetate butyrate    -   poly(styrene)        Poly(methylmethacrylate or poly(styrene maleic anhydride        copolymer) (or blends comprising one or both of these polymers)        are currently preferred for use with triazole fungicides such as        tebuconazole, cyproconazole, and epoxiconazole, for example.

It is also contemplated that certain resins such as polyalkyd resins,phenolic resins, abietic acid and epoxy resins will be suitable for thepractice of this invention. Also encompassed by the present inventionare filled polymer and co-polymer systems, i.e., using calciumcarbonate, silica, clay, and the like.

Active Ingredient. The particle of the present invention can include anactive ingredient entrapped in a polymeric matrix or a plurality ofactive ingredients having similar or different activities (e.g., afungicide and an insecticide). The active ingredient can be, forexample, any of various conventional biocides, including a fungicide(e.g., a triazole, an imidazole, a methoxyacrylate, a fungicide in themorpholine series such as fenpropimorph), a herbicide (e.g., glyphosate,phosphinothricin, triallate, alachlor), a insecticide (e.g., anorganophosphorus compound, imidacloprid, a pyrethroid), a nematocide(e.g., Tribute), an acaricide, a molluscicide, a nematocide, arodenticide, a bactericide, and a termiticide; a chemical hybridizingagent (e.g., clofenset potassium); a herbicide safener; a chemicalinducer or elicitor (e.g., a protein activator), a plant growthregulator (e.g., an auxin, a cytokinin, or a gibberellin), an elicitor,or a nutrient such as a fertilizer, or a minerals). In addition to anactive ingredient, the particle can also include one or more inertingredients such as a solvent, a dispersant, an adjuvant, or aplasticizer, and can be formulated for example as a liquid, adispersion, a water soluble granule, a wettable powder, a waterdispersible granule, a suspension concentrate, a liquid flowable, an dryflowable, a suspension, a granule, or a seed coating. Triazolefungicides suitable for the practice of this invention are exemplifiedby bitertanol, bromuconazole, cyproconazole, difenoconazole,epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol,hexaconazole, imibenconazole, metconazole, myclobutanil, penconazole,propiconazole, tebuconazole, tetraconazole, triadimefon, triadimenol,and triticonazole. Preferably the triazole fungicide is selected fromthe group consisting of cyproconazole, epoxiconazole, tebuconazole,triadimefon, and triadimenol. More preferably the triazole fungicide iscyproconazole. A discussion of the properties for some of thesefungicides can be found in U.S. Pat. No. 4,664,696, EPA 196038, and U.S.Pat. No. 4,723,984.

Some representative fungicides, herbicides, insecticides, and growthregulators that are useful in the present invention are listed below:Fungicides Benomyl Fludioxonil Benzothiadiazoles Flutolanil Captanfosetyl-Al Chlorothalonil kresoxim-Methyl Cyproconazole Mancozebcyprodinil metalaxyl epoxiconazole prochloraz fenarimol triticonazolefenpropimorph tebuconazole Bitertanol Vinclozolin BromuconazoleDifenoconazole Epoxiconazole Fenbuconazole Fluquinconazole FlusilazoleFlutriafol Hexaconazole Imibenconazole Metconazole MyclobutanilPenconazole Propiconazole Tetraconazole Triadimefon Triadimenol

Herbicides Acetochlor Acifluorfen Acrolein Alachlor Ametryn AmitroleAnilofos Asulam Atrazine Benazolin Benefin Benfluralin Bensulfuronbensulfuron-methyl Bensulfide Bentazone Bifenox Bromacil BromoxynilButachlor Butralin Butylate Carfentrazone carfentrazone-ethyl ChlorambenChlordiazon Chlorflurenol Chlorimuron Chlorotoluron ChloroxuronChlorpropham Chlorsulfuron Cinmethylin Clethodim Clomazone ClopyralidCyanazine Cycloate Cinmethylin 2,4-dichlorophenoxyacetic acid2,4-dichlorophenoxyacetic acid methyl ester Dalpon Dazomet 2,4-DB DCPADesmedipham Diallate Dicamba Diclobenil Dichlormid Dichlorprop DiclofopDiethatyl Dietholate Difenzoquat Dinoseb Diphenamid Dipropetryn DiquatDiuron EPTC Ethalfluralin Ethofumesate Fenac Fenoxaprop fenoxaprop-ethylfenuron TCA Fluazifop fluazifop-P Fluchloralin Flumetsulam FluometuronFluroglycofen fluroglycofen-ethyl Flurazole flurenol-butyl FluridoneFomesafen Fosamine Glufosinate Glyphosate Haloxyfop Halosulfuronhalosulfuron-methyl Hexazinone Imazameth imazamethazenzimazamethabenz-methyl Imazapyr Imazaquin Imazethapyr Ioxynil IsopropalinIsoproturon Isoxaben lactofen Linuron MAA MCPA MCPB Mecoprop MefenacetMefluidide Metham Methazole Metolachlor Metribuzin Metsulfuron MHMolinate Monolinuron MSMA Naproanilide Napropamide Naptalam NeburonNicosulfuron Norea Norflurazon Orbencarb Oryzalin Oxadiazon OxyfluorfenParaquat Pebulate pelargonic acid Pendimethalin phenmedipham PicloramPrimisulfuron Prodiamine Prometon Prometryn Pronamide PropachlorPropanil Propazine Propham Pyrazon pyrazosulfuron pyrazosulfuron-ethylPyridate Quizalofop quizalofop-ethyl Rimsulfuron Sethoxydim SiduronSimazine Simetryn Sulfometuron Tebuthiuron Terbacil TerbuthylazineTerbumeton Terbutryn Thifensulfuron Thiobencarb Triallate TriasulfuronTriclopyr Trifluralin Vernolate

Insecticides and Nematicides Aldicarb Fenvalerate azinphos-methylImidachloprid Carbaryl Lindanc Carbofuran Malathion Chlorpyrifos methylParathion Cyfluthrin Monocrotophos Diazinon Oftanol Dicofol OxamylDisulfoton Parathion Endosulfan Propoxur Fenamiphos Pyrethrins

Growth Regulators 6-benzyladenine Endothall alpha-naphthylactic acidEthepon Ancymidol gibberellic acid Chlorpropham maleic HydrazineDaminozide Paclobutrazol Chemical Hybridizing Agents clofenset (K⁺ salt)

Accordingly, in one embodiment the present invention comprises aparticle comprising a triazole fungicide in a polymer matrix. Forexample, the triazole fungicide can comprise a compound selected fromthe group consisting of bitertanol, bromuconazole, cyproconazole,difenoconazole, epoxiconazole, fenbuconazole, fluquinconazole,flusilazole, flutriafol, hexaconazole, imibenconazole, metconazole,myclobutanil, penconazole, propiconazole, tebuconazole, tetraconazole,triadimefon, triadimenol, and triticonazole. Preferably the triazolefungicide comprises a compound selected from the group consisting ofcyproconazole, epoxiconazole, tebuconazole, triadimefon, andtriadimenol. The polymer matrix can comprise a polymer selected from thegroup consisting of poly(methylmethacrylate), poly(lactic acid), apoly(lactic acid-glycolic acid) copolymer, cellulose acetate butyrate, apoly(styrene), hydroxybutyric acid-hydroxyvaleric acid copolymer, astyrene maleic anhydride copolymer, poly(methylvinyl ether-maleic acid),poly(caprolactone), poly(n-amylmethacrylate), wood rosin, apolyanhydride, a polyorthoester, a poly(cyanoacrylate), poly(dioxanone),ethyl cellulose, a ethyl vinyl acetate polymer, poly(ethylene glycol),poly(vinylpyrrolidone), an acetylated monogylceride, an acetylateddigylceride, an acetylated trigylceride, poly(phosphazene), chlorinatednatural rubber, a vinyl polymer, polyvinyl chloride, ahydroxyalkylcellulose, polybutadiene, polyurethane, a vinylidenechloride polymer, a styrene-butadiene copolymer, a styrene-acryliccopolymer, an alkylvinylether polymer, a cellulose acetate phthalate, anethyl vinyl phthalate, cellulose triacetate, a polyanhydride, apolyglutamate, a polyhydroxy butyrate, polyvinyl acetate, a vinylacetate-ethylene copolymer, a vinyl acetate-vinylpyrrolidone copolymer,an acrylic polymer, an alkyl acrylate polymer, an aryl acrylate polymer,an aryl methacrylate polymer, a poly(caprolactam), an epoxy resin, apolyamine epoxy resin, a polyamide, a polyvinyl alcohol polymer, apolyalkyd resin, a phenolic resin, an abietic acid resin, a silicone, apolyalkylene oxide, and a polyester.

The particle of the present invention can further comprise otheringredients including inert ingredients. For example, the inventiveparticle can comprise a plasticizer.

The present invention can comprise a particle having a variety ofdiameters or average diameters. For example, the mean diameter of theparticle can be in the range of from about 0.1 microns to about 200microns, preferably from about 0.2 microns to about 100 microns, andmore preferably from about 0.5 microns to about 50 microns.

Release of Active Ingredient from the Particle. The particle accordingto the present invention can release an agricultural chemical in acontrolled fashion by diffusion (e.g., in the case of a particle havinga polymer matrix comprising poly(methylmethacrylate or poly(styrenemaleic anhydride copolymer) or by disintegration or dissolution of thematrix (e.g., in the case of a particle having a polymer matrixcomprising polylactic acid polymers), depending on the matrix polymeremployed. Release rates also vary with the size of particles (i.e.,release rates vary as a function of the surface area/volume ratio of theparticle). The matrix material can be selected to have propertiesconducive to the appropriate release and action of the agriculturallyactive ingredient in space and time. A particle can also be preparedsuch that the active ingredient varies in concentration from the outersurface of the matrix particle to its core, providing “programmed” ratesand levels of active release over the duration of the seed germinationand subsequent growth periods.

The rate of release of an active ingredient from a particle according tothe present invention depends on the polymer, size of the particle, theloading of the active ingredient, and the dispersing agent used, if any.The manner in which an active ingredient can be released from a particledepends on whether the loaded active ingredient is suspended ordissolved in the matrix. The steps involved when the active ingredientis dissolved in the matrix material include: diffusion of the activeingredient to the surface of the matrix; partition of the activeingredient between the matrix and the environment or elution medium(e.g., soil water, seed coat, or foliar surface); and transport awayfrom the particle surface. In addition, if the active ingredient isdispersed (for example, as multimolecular pockets of active ingredientin the particle), the active ingredient may have to dissolve into thematrix material before diffusion to the surface.

Another mode of release of the active ingredient can be bybiodegradation or erosion of the matrix material, the rate of which canbe influenced by the hydrophobicity or hydrophilicity of the polymer,the morphology of the particle, and the chemical nature of the polymercomprising the matrix for example. In addition, the active ingredientcan be released by swelling of the polymer matrix after imbibition of aliquid such as water. In diffusion-controlled systems the matrix may beunaffected by swelling, but in swelling-controlled systems the polymermatrix may undergo a transition from a glassy state to a gel state uponinteraction with the penetrating solvent. In such cases, release ratecan be a function of the glass-to-gel transition process.

Another factor affecting release rate is osmotic pressure, which can becreated inside the particle if the active ingredient or polymer has anaffinity for the environment external to the particle. The activeingredient is released when the osmotic pressure exceeds the maximumforce that the matrix of the particle can tolerate.

Mathematical models for these release mechanisms are described in thefollowing individual references:

U. Pothakamury and G. Barbosa-Canovas, Trends in Food Science &Technology 6:397-406, 1995.

R. Langer and N. Peppas, JMS-Rev. Macromol. Chem. Phys. C(23):61-126,1983.

Formulations Including the Particle. The particle according to theinvention can be used according to any conventional formulation,including but not limited to: a suspension or slurry of particles in anaqueous medium (e.g., water) at a concentration of active ingredient offrom about 0.5% to 99%, preferably 5-40% based on the weight of theparticle, for storage and shipping; wettable powders, wettable granules(dry flowable), and dry granules. If formulated as a suspension orslurry, the concentration of the active ingredient in the formulation ispreferably about 0.5% to about 99% by weight (w/w), preferably 5-40%.

Other conventional inactive or inert ingredients can be incorporatedinto the particle or in aqueous media used for producing suspensions ofthe particle according to the present invention. Such inert ingredientsinclude but are not limited to: conventional sticking agents, dispersingagents such as methylcellulose (Methocel A15LV or Methocel A15C, forexample, serve as combined dispersant/sticking agents for use in seedtreatments), polyvinyl alcohol (e.g., Elvanol 51-05), lecithin (e.g.,Yelkinol P), polymeric dispersants (e.g., polyvinylpyrrolidone/vinylacetate PVP/VA S-630), thickeners (e.g., clay thickeners such as Van GelB to improve viscosity and reduce settling of particle suspensions),emulsion stabilizers, surfactants, antifreeze compounds (e.g., urea),dyes, colorants, and the like. Further inert ingredients useful in thepresent invention can be found in McCutcheon's, vol. 1, “Emulsifiers andDetergents,” MC Publishing Company, Glen Rock, N.J., U.S.A., 1996.Additional inert ingredients useful in the present invention can befound in McCutcheon's, vol. 2, “Functional Materials,” MC PublishingCompany, Glen Rock, N.J., U.S.A., 1996.

Formulations according to the present invention can be applied by anyconventional method, including but not limited to: (1) direct injectioninto the soil around seeds or in the root zone of developing plants, forexample, at a point 2 cm deep and within a 3 cm radius of the plantcrown; (2) application as a soil drench; (3) application as a foliarspray; and (4) application as a seed treatment.

Particles according to the present invention can be applied to seeds byany standard seed treatment methodology, including but not limited tomixing in a container (e.g., a bottle or bag), mechanical application,tumbling, spraying, and immersion. Any conventional active or inertmaterial can be used for coating seeds with particles according to thepresent invention, such as conventional film-coating materials includingbut not limited to water-based film coating materials such as Sepiret(Seppic, Inc., Fairfield, N.J.) and Opacoat (Berwind Pharm. Services,Westpoint, Pa.).

The formulated product, when used as a suspension in an aqueous carrier,preferably comprises a dispersing agent to permit a relatively uniformor homogeneous mixture to form. The dispersing agent preferably alsoprovides a degree of “tackiness” or adhesion to the particle formulationin order for the formulation to adhere to treated seeds-or other foliarsurfaces. Suitable dispersing agents include but are not limited toaqueous 0.25-1.0% poly(vinyl alcohol), such as Elvanol 51-05 (DuPont)and Methocel A15LV.

One embodiment of the present invention provides a fungicidalcomposition comprising a particle comprising a triazole fungicide in apolymer matrix, and an agricultural adjuvant. The composition can take avariety of forms, including a liquid suspension, a wettable powder, agranule, a water-dispersible granule, a suspension concentrate, or thelike. Preferably, the fungicidal composition comprises a dispersant. Thefungicidal composition also preferably comprises an adjuvant. Thefungicidal composition can also comprise a diluent. The diluent can beeither a solid or a liquid diluent. Solid diluents can include, forexample, silica, alumina, cellulose, methylcellulose, clay, or apolymer. Liquid diluents can include, for example, water, an organicsolvent, or an inorganic solvent.

Methods of producing matrix particles. The matrix particles of thepresent invention can be produced by any process that results in apolymer matrix having active ingredients substantially uniformlydistributed therein, including but not limited to solvent evaporation,solvent partition, hot melt microencapsulation, coacervation, emulsionpolymerization, interfacial polycondensation, and spray drying.

A preferred process for entrapping the agriculturally active ingredientin accordance with the present invention includes the following steps:

(A) Preparation of a hydrophobic solution (“oil phase”) including anactive ingredient and a polymer in an organic solvent;

(B) Preparation of a hydrophilic solution (“aqueous phase”) bydissolving a dispersing agent in water (or an aqueous or alcoholicsolution);

(C) Forming an emulsion by combining the hydrophobic solution with thehydrophilic solution with stirring, homogenization, or sonication;

(D) Stirring the emulsion formed in (C) until all of the organic solventhas evaporated. The organic solvent can alternatively or additionally beremoved at reduced pressure using a rotary evaporator; and

(E) Optionally isolating the matrix particles by allowing the evaporatedemulsion formed in (D) to settle, decanting the supernatant liquid fromthe matrix particles, then washing, filtering, and drying the particlesin air.

The particles can be resuspended in an aqueous carrier system comprisingwater and, for example, a dispersing agent, dye or colorant, or otherinert ingredient. The particles can alternatively be used withoutisolation.

Specifically, the matrix particle preparation process can be carried outby dissolving the agriculturally active ingredient and the polymer in anamount of organic solvent sufficient to form the hydrophobic solution.This dissolution is performed at room temperature or at temperatures notgreater than 50° C. with mechanical stirring. For microencapsulatingactive ingredients according to this general process, it is preferredthat the active ingredient be preferentially soluble in the hydrophobicphase rather than in the hydrophilic phase, and preferably substantiallyinsoluble in the aqueous phase (by substantially insoluble is meant asolubility of less than 1% by weight in water at 25° C.). A dispersingagent can then be dissolved in a quantity of deionized water sufficientto form the hydrophilic solution. This dissolution is performed at roomtemperature with mechanical stirring. The hydrophobic solution is thenpoured into the hydrophilic solution, while stirring, homogenizing, orsonicating the hydrophilic solution vigorously to form an emulsion, orby any other method conventionally used in the emulsification art. Theemulsion comprises microdroplets from the hydrophobic solution that areuniformly dispersed and suspended in the hydrophilic solution. Thedroplet size and the final size of the matrix particle is controlled byshear rate and degree of agitation, the temperature, the volumetricratio of the dispersed hydrophobic phase to continuous aqueous phase,and the type of dispersing agent used, if any. Stirring of the emulsioncan be continued until all of the organic solvent is evaporated. Oncethe organic solvent has evaporated, the supernatant liquid can bedecanted and the matrix particles can be washed, filtered, and dried orused, preferably as is.

In the process outlined above, the organic solvent used to prepare thehydrophobic solution should be suitable for co-dissolving the requiredamounts of the active and polymer to form a hydrophobic(water-immiscible) solution. The organic solvent should not otherwiseinteract with or alter the intended functions of the active or polymerin the prepared matrix particles. The organic solvent should also haveadequate volatility at room temperature (sufficiently low boiling pointat ambient pressures) in order to evaporate at a reasonable rate fromthe emulsion. The solvent in the method of the present invention ispreferally a substantially hydrophobic solvent. For example, the solventcan comprise a compound selected from the group consisting ofhalogenated hydrocarbons, aromatic compounds, hydrocarbons, ethers, andesters. Methylene chloride is an example of an organic solvent suitablefor the practice of this invention. Other suitable organic solventsinclude but are not limited to ethyl acetate, chloroform,carbontetrachloride, acetonitrile, diethyl ether, dimethyl ether, acetone,methylethylketone, pentane, hexane, hexanes, heptane, dioxane, ethanol,methanol, pyridine, propanol, 2-propanol, butanol, 2-butanol, t-butylalcohol, isobutyl alcohol, perchloroethylene, tetrachloroethane,o-xylene, m-xylene, p-xylene, toluene, benzene, mesitylene,chlorobenzene, o-dichlorobenzene, m-dichlorobenzene, p-dichlorobenzene,or any other organic solvent which is chemically unreactive under theparticle-forming conditions and which is capable of being evaporatedunder temperature or pressure conditions under which the particle of thepresent invention is stable. Preferably the solvent comprises a compoundselected from the group consisting of methylene chloride, o-xylene,m-xylene, p-xylene, toluene, and chlorobenzene. More preferably thesolvent comprises methylene chloride. The amount of organic solventuseful in forming the hydrophobic solution ranges from about two toabout eight times, and preferably about three times, the weight of thepolymer (or of the combined weight of the polymer and the active).

In general, no adjustment of the pH of the system is required during thematrix particle process to achieve satisfactory performance andproduction of entrapped material.

A preferred process for producing matrix particle of the presentinvention utilizes solvent evaporation. Briefly, the solvent evaporationtechnique involves mixing a hydrophobic liquid medium and a hydrophilicliquid medium to produce an emulsion. An emulsion can be made with ahydrophobic phase in a hydrophilic phase (e.g., oil-in-water) or with ahydrophilic phase in a hydrophobic phase (e.g., water-in-oil); theformer is currently preferred. Moreover, it is preferred to produce anemulsion in which the volume of the hydrophilic phase is significantexcess to the volume of the hydrophobic phase. An active ingredient canbe added that preferentially dissolves in the hydrophobic phase, andpreferably is substantially insoluble in the hydrophilic phase. Theshear rate and time period for mixing the hydrophobic and hydrophilicphases is selected so as to produce uniformly dispersed hydrophobicdroplets having average diameters in the range from about 0.2 to 200microns, preferably from about 1 to about 50 microns. The solvent isthen evaporated from the hydrophobic phase, producing matrix particlesof the present invention.

In the solvent partition technique, an active ingredient is dissolved ordispersed in a volatile organic solvent. The resulting solution issuspended as a fine dispersion in an organic oil into which the organicsolvent is extracted to produce particles. This technique can be carriedout at room temperature and does not require water. As one example, apolymer is dissolved in methylene chloride, the required amount of anactive ingredient (e.g., a fungicide) is added, and the mixture issuspended in silicone oil containing a nonionic emulsifier such as Span85 and additional methylene chloride. After adding the polymer solutionto the silicone oil, petroleum ether is added and the mixture is stirreduntil the matrixed particles have hardened. The particles can be removedby filtration or centrifugation, washed with petroleum ether, and driedunder vacuum. Examples of the solvent partition technique are providedin R. Langer et al., Polymer 31:547-555,1990. Further examples of thesolvent partition technique are provided in Kirk-Othmer Encyclopedia ofChemical Technology, fourth edition, vol. 16, Curt Thies.

In hot melt microencapsulation(;), a polymer melt is mixed with theactive ingredient, which can be suspended or dissolved therein. Theresulting mixture is suspended in a nonmiscible solvent (for example,silicone oil or olive oil) that is heated about 5° C. above the meltingpoint of the polymer while stirring continuously. After an emulsion isformed and stabilized, it is cooled until the particles are solidified.After cooling, the particles are washed by decantation with petroleumether to produce a free-flowing powder. In general, the resultingparticles are less than about 50 microns in diameter. Examples of thehot melt microencapsulation technique are provided in E. Mathiowitz andR. Langer, J. Contr. Rel. 5:13-22, 1987. Further examples of the hotmelt microencapsulation technique are provided in Microcapsules andNanoparticles in Medicine and Pharmacy, ed. M. Donbrow, CRC Press, 1992,pp. 105-107.

In one embodiment, the present invention provides a method of producinga particle wherein the particle comprises a triazole fungicide in apolymer matrix comprising providing a hydrophobic solution comprising atriazole fungicide, a polymer, and a solvent; mixing the hydrophobicsolution and an aqueous medium to produce a dispersion of droplets ofthe hydrophobic solution in the aqueous medium; and evaporating thesolvent from the dispersion to produce a particle comprising a triazolefungicide in a polymer matrix. Preferably the fungicide is a triazolefungicide such as bitertanol, bromuconazole, cyproconazole,difenoconazole, epoxiconazole, fenbuconazole, fluquinconazole,flusilazole, flutriafol, hexaconazole, imibenconazole, metconazole,myclobutanil, penconazole, propiconazole, tebuconazole, tetraconazole,triadimefon, triadimenol, or triticonazole. More preferably thefungicide is selected from the group consisting of cyproconazole,epoxiconazole, tebuconazole, triadimefon, and triadimenol.

Preferably the polymer is selected from the group consisting ofpolystyrene-maleic anhydride copolymer or polymethylmethacrylate.

The hydrophobic solution of the present method can comprise a dispersingagent.

The hydrophilic solution in the method of the present invention can alsocomprise a dispersing agent. Preferably the dispersing agent in thehydrophilic solution is methyl cellulose or polyvinyl alcohol.

The solvent evaporation step of the method of the present invention cancomprise applying vacuum, heat, or a combination of vacuum and heat tothe dispersion. Alternatively, the solvent evaporation step can compriselyophilizing the dispersion.

Application of matrix particles to soil, seed, or plant. The particleand formulation composition of the present invention can be applied tothe soil, where the active ingredient can be released and eventuallyaffect a target pest either directly or indirectly. For example, theactive ingredient can be taken up by a plant, or taken up by ordistributed to a part of which is ingested or infested by the pest.

The particle formulation can be applied by any conventional method,including but not limited to: (1) injection of a formulation (e.g., anaqueous suspension of particles) directly into the soil around seeds orin the root zone of developing plants (e.g., injection at a point 2 cmdeep and within a 3 cm radius of the plant crown; (2) application as asoil drench to the point at which the soil is at field capacity; (3)application as a foliar spray, preferably in a sufficient volume tothoroughly wet the foliage; and (4) application directly to seeds (i.e.,seed treatment). Release of the active ingredient from the particle willprovide a desired biological effect in the zone of application or uponuptake of the active ingredient by the plant.

A particle or formulation of the present invention can be applied toseed by any standard seed treatment methodology, for example, by using aHege 11 Liquid Seed Dresser.

Matrix particles of the present invention can be applied in combinationwith another active ingredient that is provided as fast- or slow-releaseformulations. Slow-release matrix particles according to the presentinvention can also be applied together with a fast-release formulationhaving the same active ingredient (or with a particle comprising thesame active ingredient) in order to achieve, for example, a chemicalapplication regime with an initial high rate of release followed by aslower rate of release over a longer period of time.

The treatment method of the present invention provides, for example amethod for the treatment or prophylaxis of a fungal disease in a targetplant wherein the method comprises contacting a plant cell, a planttissue, or a seed with a particle wherein the particle comprises atriazole fungicide in a polymer matrix. Preferably the treatment methodcomprises contacting a seed with the particle of the present invention.Preferably the contacting is performed before the seed is planted.Preferably the triazole fungicide is selected from the group consistingof bitertanol, bromuconazole, cyproconazole, difenoconazole,epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol,hexaconazole, imibenconazole, metconazole, myclobutanil, penconazole,propiconazole, tebuconazole, tetraconazole, triadimefon, triadimenol,and triticonazole. More preferably the fingicidal agent is selected fromthe group consisting of cyproconazole, epoxiconazole, tebuconazole,triadimefon, and triadimenol.

The polymer matrix useful in the treatment method of the presentinvention preferably comprises a polymer selected from the groupconsisting of poly(methylmethacrylate), poly(lactic acid), a poly(lacticacid-glycolic acid) copolymer, cellulose acetate butyrate, apoly(styrene), hydroxybutyric acid-hydroxyvaleric acid copolymer, astyrene maleic anhydride copolymer, poly(methylvinyl ether-maleic acid),poly(caprolactone), poly(n-amylmethacrylate), wood rosin, apolyanhydride, a polyorthoester, a poly(cyanoacrylate), poly(dioxanone),ethyl cellulose, a ethyl vinyl acetate polymer, poly(ethylene glycol),poly(vinylpyrrolidone), an acetylated monogylceride, an acetylateddigylceride, an acetylated trigylceride, poly(phosphazene), chlorinatednatural rubber, a vinyl polymer, polyvinyl chloride, ahydroxyalkylcellulose, polybutadiene, polyurethane, a vinylidenechloride polymer, a styrene-butadiene copolymer, a styrene-acryliccopolymer, an alkylvinylether polymer, a cellulose acetate phthalate, anethyl vinyl phthalate, cellulose triacetate, a polyanhydride, apolyglutamate, a polyhydroxy butyrate, polyvinyl acetate, a vinylacetate-ethylene copolymer, a vinyl acetate-vinylpyrrolidone copolymer,an acrylic polymer, an alkyl acrylate polymer, an aryl acrylate polymer,an aryl methacrylate polymer, a poly(caprolactam), an epoxy resin, apolyamine epoxy resin, a polyamide, a polyvinyl alcohol polymer, apolyalkyd resin, a phenolic resin, an abietic acid resin, a silicone, apolyalkylene oxide, and a polyester.

Preferably after the contacting step, the health of the target plant issubstantially similar to the health of a control plant which issubstantially free of the fungal disease and which is free of contactwith the triazole fungicide. Alternatively, the health of the targetplant after the contacting step is intermediate between the health of afirst control plant which is substantially free of the fungal diseaseand which is free of contact with the triazole fungicide, and the healthof a second control plant which is substantially free of the fungaldisease and which is contacted with the triazole fungicide in theabsence of the polymer matrix.

EXAMPLES Example 1

3.72 g of cyproconazole (96.3% purity; Sandoz Agro, Ltd., Basel,Switzerland) and 14.3 g of polylactic acid (Chronopol 95; Chronopol,Golden, Colo.) were dissolved in 156 g methylene chloride (Burdick &Jackson, Muskegon, Mich.) in a glass bottle with shaking to produce ahydrophobic solution.

7.5 g of polyvinyl alcohol (Elvanol 51-05; DuPont, Wilmington, Del.))was dissolved with stirring in deionized water to produce 1500 g ofhydrophilic solution.

The hydrophobic solution was added to the hydrophilic solution and themixture was vigorously stirred to produce an emulsion. The stirringcontinued for one hour. Microscopic examination of the appearance andsize of the oil droplets in the emulsion showed that the average size ofoil droplets was in the 30-50 micrometer (micron, μ) range.

The emulsion was then transferred to a two liter (L) round bottom flankand attached to a rotary evaporator to remove the methylene chloride ata reduced pressure. The final methylene chloride residue was removed byheating the flask in a hot water bath at 40° C. while on the evaporator.

The resulting particle suspension was filtered on a Buechner funnel toproduce a filter cake, which was washed with three portions of deionizedwater to remove the last traces of aqueous filtrate. The filter cake wasthen air dried by spreading the product out on a sheet of clean paper.

An aqueous carrier solution was prepared by dissolving urea (FischerScientific, Pittsburgh, Pa.) and Methocel® A15LV (Dow Chemical Co.,Midland, Mich.) in water by stirring. Urea was added as an anti-freezeand Methocel A15LV as a combined dispersant and non-phytotoxic stickingagent for use in seed treatments. (A clay thickener such as Van Gel® B(R. T. Vanderbilt Co., Inc., Norwalk, Conn.) are optionally added to theaqueous carrier solution to improve viscosity and reduce settling.) Thedry microcapsules were stirred into the aqueous carrier solution toproduce a homogenous suspension.

The composition of the final formulation (Formulation 1) is shown below.Formulation 1 Weight Ingredients % w/w (g) Active Ingredient (“a.i.”)Cyproconazole (19.88%) 17.72 37.32 7.42 g (% a.i. (w/w) = 3.52) Urea4.49 9.46 Methocel ® A15LV 0.05 1.05 Water, deionized 77.29 162.79 Total100.00% 210.62 % polymer (w/w) = 14.2

Example 2

1.56 g cyproconazole (96.3% purity) and 13.44 g cellulose acetatebutyrate polymer (Sigma Chemical Co., St. Louis, Mo.) were dissolved in82.22 g methylene chloride in a glass bottle with shaking to produce ahydrophobic solution. 1.00 g of Methocel® A15LV and 20 g of urea weredissolved in 64 g deionized water to prepare 85 g of a hydrophilicsolution. The hydrophobic solution was added to the hydrophilic solutionwith stirring to produce an emulsion. The emulsion was stirred for 5minutes to equilibrate. To reduce the particle size further, theemulsion was sonicated for 5.5 minutes with a sonic dismembrator (Model550, Fischer Scientific, Pittsburgh, Pa.) using a variable power range.Cooling was provided by an ice bath to keep the temperature below 30° C.Microscopic examination showed particles mainly in the 4-5 micron range.The emulsion was transferred to a rotary evaporator and methylenechloride stripped off as described in Example 1. The resulting productwas passed through a #325 mesh sieve to remove foreign particles andassayed for particle size, density (at room temperature), and % activeingredient.

The following were the properties of the matrix particles (Formulation2): Formulation 2 - Properties % active ingredient 1.72 (w/w) Density,g/mL 1.11 Ave. particle size, μ 4.4

Example 3

Following the general procedure of Example 2, matrix particlesuspensions having the compositions given below were produced. ForFormulation 3, methylene chloride was evaporated with stirring atatmospheric pressure. For Formulation 4, Formulation 5, Formulation 6,and Formulation 7, methylene chloride was evaporated with a rotaryevaporator at reduced pressure. For Formulation 7, Van Gel® B was addedas part of the aqueous carrier medium. Poly(methylmethacrylate) (PMM)and polystyrene (50,000 MW) were obtained from Polysciences Inc.(Warrington, Pa.) Weight % of Ingredients Formulation Number Ingredients3 4 5 6 7 Cyproconazole* 1.50 1.50 3.00 3.00 3.00 Chronopol 95 13.5013.50 — — — PMM — — 6.00 12.00 6.00 Polystyrene — — 6.00 — 6.00 MethocelA15LV 1.00 1.00 1.06 1.06 — Urea 20.00 20.00 — — — Van Gel B — — — —3.40 Water 64.00 64.00 83.94 83.94 81.60 Total 100.00 100.00 100.00100.00 100.00*100% a.i. basis. Compensate for purity with polymer.

The matrix particle suspensions had the following properties:Formulation Properties 3 4 5 6 7 Density 1.10 1.12 1.02 1.04 1.02 R.T.,g/mL Ave. particle 1.18 2.52 1.84 1.13 138.50 size, μm Viscosity* atspindle # spindle # spindle # spindle # spindle # room 18 18 18 18 31temperature, cps R.P.M. - 60 11.30 27.90 9.52 16.70 185 R.P.M. - 3012.40 28.60 9.92 17.00 329 R.P.M. - 12 15.50 32.60 11.00 17.00 765R.P.M. - 6 22.00 36.10 13.50 21.00 1520*Viscosity in centipoise (cps) was determined using a Brookfieldviscometer (model LVT, Brookfield Engineering Laboratories, Stoughton,MA) according to manufacturer instructions).

Example 4

Following the general procedure of Example 2, matrix particlesuspensions having the compositions given below were produced: Weight %of Ingredients Formulation Ingredients 5 8 9 Cyproconazole* 3.00 3.003.00 Chronopol 95 — — 6.00 PMM 6.00 6.00 — Polystyrene 6.00 6.00 6.00Methocel A15LV 1.06 1.00 1.00 Van Gel B — 2.06 2.06 Water 83.94 81.9483.94 Total 100.00 100.00 100.00*100% a.i. basis. Compensate for purity with polymer.

The matrix particle suspensions were analyzed for the followingproperties: Formulation Properties 5 8 9 Density, R.T., g/mL 1.02 1.041.04 Ave. particle size, μ 1.84 2.06 6.15 Viscosity at room spindle # 18spindle # spindle # 18 temperature, cps 18 R.P.M.* - 60 9.52 22.70 21.70R.P.M.* - 30 9.92 26.20 22.90 R.P.M.* - 12 11.00 34.60 25.40 R.P.M.* - 613.50 41.60 27.00*Revolutions per minute.

Example 5

Following the general procedure of Example 2, matrix particlesuspensions having the compositions given below were produced. Thehydrophilic and hydrophobic solutions were sonicated to produce anemulsion for preparation of Formulation 8 and homogenized with aSilverson L4R laboratory homogenizer (Silverson Machines, Inc., EastLongmeadow, Mass.) to produce and emulsion for preparation ofFormulation 10 and Formulation 11. Weight % of Ingredients FormulationIngredients 8 10 11 Cyproconazole* 3.00 3.00 3.00 PMM 6.00 6.00 6.00Polystyrene 6.00 6.00 6.00 Methocel A15LV 1.00 1.00 1.00 Van Gel B 2.062.06 3.00 Water 81.94 81.94 81.00 Total 100.00 100.00 100.00*100% a.i. basis. Compensate for purity with polymer.

The matrix particle suspensions had the following properties:Formulation Properties 8 10 11 Density, R.T., g/ml 1.04 1.04 1.05 Ave.particle size, μm 2.06 3.55 3.20 Viscosity at room spindle # 18 spindle# 18 spindle # 31 temperature, cps R.P.M. - 60 22.70 47.40 192 R.P.M. -30 26.20 52.40 265 R.P.M. - 12 34.60 61.80 446 R.P.M. - 6 41.60 74.60685^(a)Gel structure.

Example 6

Following the general procedure of Example 2, matrix particlesuspensions having the compositions in the table below were produced.The hydrophilic and hydrophobic solutions were homogenized in a coolingbath in preparing Formulation 12 and Formulation 13, but not inpreparing Formulation 10 and Formulation 14. Weight % of IngredientsFormulation Ingredients 10 14 12 13 Cyproconazole* 3.00 3.00 3.00 3.00PMM 6.00 6.00 6.00 6.00 Polystyrene 6.00 6.00 6.00 6.00 Methocel A15 C —0.75 1.75 0.75 Methocel A15LV 1.00 — — — Van Gel B 2.06 — — — Water81.94 84.25 83.25 84.25 Total 100.00 100.00 100.00 100.00*100% a.i. basis. Compensate for purity with polymer

The matrix particle suspensions were analyzed for the followingproperties: Formulation Properties 10 14 12 13 Density, R.T., g/mL 1.041.02 1.02 1.03 Ave. particle size, μ 3.55 69.51 11.00 55.56 Viscosity atroom spindle # spindle # spindle # 34 spindle # temperature, cps 18 3131 R.P.M - 60 47.40 97.70 980 82.70 R.P.M - 30 52.40 101.00 1020 86.80R.P.M - 12 61.80 105.00 1060 87.70 R.P.M - 6 74.60 125.00 1150 95.20

Example 7

Following the general procedure of Example 1, matrix particlesuspensions having the compositions given below were produced. In thetable below, runs designated (a) employed particle preparations thatwere not filtered, washed and dried after solvent evaporation, runsdesignated (b) employed particles that had been filtered, washed, andair dried as described in Example 1. Weight % of Ingredients (b) (a) (b)(a) (b) Formulation Ingredients 15 16 17 18 19 Cypro- 3.52 3.52 3.523.52 3.52 conazole* Polymer** 14.22 (1) 13.56 (2) 13.62 (2) 13.56 (3)14.70 (3) Urea 4.49 4.50 4.46 4.50 4.46 Methocel 0.50 0.50 0.47 0.500.49 A15LV Water 77.29 77.92 77.93 77.92 76.83 Total 100.00 100.00100.00 100.00 100.00*100% a.i. basis. Compensate for purity with polymer**(1) Chronopol 95; (2) cellulose acetate butyrate; (3) poly(methylmethacrylate).

The matrix particle suspension were analyzed for the followingproperties: Formulation Properties 15 16 17 18 19 % a.i. 3.19 3.62 3.474.41 3.53 Ave. particle 40.00 193.00 75.00 22.80 70.00 size, μm

The formulations produced in this Example were applied to wheat asfollows. Wheat seed was weighed out into 50 g batches for eachtreatment. Stock solutions were prepared by weighing out the formulationand adding deionized water to prepare stock solutions of the high ratefor each formulation, then, dilutions were prepared from these stocks toprovide various rates of application.

A Hege 11 laboratory scale rotostatic seed treater with a 200-gram smallcapacity seed treatment drum was used for the seed treatments.

For each treatment, a sample batch of seed was treated with theformulation or with the solvent alone to wet up/dirty the drum asrecommended by the manufacturer. This seed sample was then discarded.The treatment was then drawn up into a syringe and slowly applied to anew 50 g batch of seed in the seed treater. As soon as the seed appeareddry (usually about 30-45 seconds), it was transferred into a 1 L plasticbeaker. The seed was then transferred to a 4 oz. glass jar for storage.The lid of the jar was left off for several hours to ensure that theseed was totally dry. The treatments were applied in order from thelowest rate to the highest rate for each formulation. After the highestrate for each formulation, the seed treater was thoroughly scrubbed outwith absolute ethanol on a paper tissue to prevent contamination of thenext formulation. The syringe, funnel and beaker were also rinsed withethanol. This procedure was repeated for each of the formulations thatwere tested.

At the end of all the treatments and/or when active ingredients werechanged in the course of the same study, we also used an additional stepof cleaning with a solution of soap in water and an additional ethanolwipe.

In order to assess the safety of the formulations, wheat seed that hadbeen treated previously with test formulations was seeded in standard4″-square pots containing sterilized Dupo silt loam soil. Seeding wasdone at a rate of 12-25 seeds per pot, with four replicate pots of eachtreatment rate. Seeds were covered with approximately 2 cm of the samesoil and incubated under a 12-hour photoperiod, 50% relative humidity at18° C. Eight to twelve days after planting (DAP), each replicate pot ofeach treatment was rated for the number of seedlings emerged and theaverage height of emerged seedlings was estimated. The main indicator offormulation performance was the measure of seedling height relative tountreated control plants (untreated=100%).

The table below shows and FIG. 1 illustrates the safety of thesetreatments, expressed as the height of germinating wheat at 9 days afterplanting (DAP) as a percent of the height of untreated controls. Forcomparison, Alto 005LS (Sandoz Agro, Ltd., Basel, Switzerland) wasincluded as a standard, fast-release non-matrix formulation liquid seedtreatment of cyproconazole. Height of Percent Intended AnalyticalPredicted Treated of Rate Percent Rate (g Plant in Control (g/100 kgRecovery of a.i./100 kg cm (9 Height (9 Rep. No. Formulation Seed)Applied seed) DAP) DAP) 1-1  ALTO 1.1 9.6 82 005LS 1-2  ALTO 4.4 98.44.3296 7.5 64 005LS 1-3  ALTO 8.8 93.1 8.1928 6.5 55 005LS 1-4  ALTO17.6 90.5 15.928 4.0 33.5 005LS 1-5  15 1.1 10.4 88.6 1-6  15 4.4 75.73.3308 9.0 76.5 1-7  15 8.8 75.6 6.6528 8.5 72.5 1-8  15 17.6 70.512.408 8.4 71.5 1-9  15 35.2 261 91.872 3.7 31.6 1-10 18 1.1 10.8 921-11 18 4.4 79.8 3.5112 9.4 79.8 1-12 18 8.8 83.6 7.3568 9.4 80.3 1-1318 17.6 97 17.072 8.1 68.5 1-14 19 1.1 11.5 98 1-15 19 4.4 66.6 2.930410.2 86.9 1-16 19 8.8 63.2 5.5616 9.7 82.6 1-17 19 17.6 67 11.792 8.673.4 1-18 16 1.1 10.1 86.3 1-19 16 4.4 76.6 3.3704 10.1 85.6 1-20 16 8.867.7 5.9576 9.3 79.2 1-21 16 17.6 65.1 11.4576 9.0 76.1 1-22 17 1.1 10.589.2 1-23 17 4.4 89.8 3.9512 9.6 81.3 1-24 17 8.8 101 8.888 8.9 75.31-25 17 17.6 90.5 15.928 8.7 73.6 1-26 82 1.1 9.2 78.6 1-27 82 4.4 106.14.6684 8.2 69.4 1-28 82 8.8 101.1 8.8968 7.0 59.4 1-29 82 17.6 98.417.3184 5.7 48 1-30 Untreated 0 9.2 100 Check

Example 8

Following the general procedure of Example 2, matrix particlesuspensions having the following compositions were produced. Celluloseacetate butyrate was obtained from Sigma Chemical Co. (St. Louis, Mo.).SMA 1440A resin, an ester/styrene maleic anhydride copolymer, wasobtained from Sartomer Co. (West Chester, Pa.). Poly(methyl vinylether/maleic acid) was obtained from Sigma Chemical Co. (St. Louis,Mo.). Weight % of Ingredients Formulation Ingredients 20 21 22 23 24Cyproconazole* 1.50 1.50 1.50 1.50 1.50 Cellulose acetate 6.75 — — 6.75— butyrate SMA ® 1440A 6.75 13.50 — — Resin Wood rosin — — 13.50 — —Poly (methyl vinyl — — — 6.75 — ether/maleic acid) PMM — — — — 13.50Methocel A15C 1.00 1.00 1.00 1.00 1.00 Water 84.00 84.00 84.00 84.0084.00 Total 100.00 100.00 100.00 100.00 100.00*100% a.i. basis. Compensate for purity with polymer

The suspensions produced in this Example were applied to wheat using theprocedure set forth in Example 7. The table below shows and FIG. 2illustrates the safety of these treatments at 10 days after planting ascompared to Alto 005LS. Height of Intended Analytical Predicted TreatedPercent of Rate Percent Rate (g Plant in Control (g/100 kg Recovery ofa.i./100 kg cm (9 Height (9 Rep. No. Formulation Seed) Applied seed)DAP) DAP) 2-1  ALTO 1.1 122.7 1.35 8.2 80.4 005LS 2-2  ALTO 4.4 114.15.02 6.6 64.9 005LS 2-3  ALTO 8.8 91 8.01 5.0 49.0 005LS 2-4  ALTO 17.693.7 16.49 3.5 34.5 005LS 2-5  20 1.1 81.3 0.89 9.0 87.9 2-6  20 4.485.2 3.75 8.0 78.4 2-7  20 8.8 78.2 6.88 7.3 70.7 2-8  20 17.6 73.212.88 6.2 60.2 2-9  21 1.1 91.8 1.01 9.0 87.8 2-10 21 4.4 68.4 3.01 7.876.4 2-11 21 8.8 75.2 6.62 7.1 69.1 2-12 21 17.6 83 14.61 5.0 49.1 2-1322 1.1 80.9 0.89 8.7 84.6 2-14 22 4.4 70.2 3.09 7.5 72.7 2-15 22 8.8 766.69 6.8 66.2 2-16 22 17.6 78.9 13.89 5.3 51.9 2-17 23 1.1 120 1.32 8.380.9 2-18 23 4.4 98.9 4.35 7.5 73.4 2-19 23 8.8 62.7 5.52 7.3 71.3 2-2023 17.6 99.3 17.48 4.4 42.3 2-21 24 1.1 240 2.64 8.6 83.7 2-22 24 4.4124.5 5.48 8.5 83.3 2-23 24 8.8 126 11.09 7.5 73.3 2-24 24 17.6 10919.18 7.7 75.3 2-25 Untreated 0 0 10.3 100.0 Check

Example 9

Following the general procedure of Example 1, matrix particlesuspensions having the following compositions were produced. LactelBP-400 was obtained from Sigmal Chemical Co. (St. Louis, Mo.). Weight %of Ingredients Formulations Ingredients 25 26 Cyproconazole* 3.0 3.0Lactel BP-400 — 12.0 Cellulose acetate 12.0 — butyrate Methocel A15LV1.0 1.0 Water 84.0 84.0 Total 100.0 100.0*100% a.i. basis. Compensate for purity with polymer.

The suspensions produced in this Example were applied to wheat using theprocedure set forth in Example 7. The table below shows and FIG. 3illustrates the safety of these treatments at 10 days after planting ascompared to Alto 005LS. Rate (g Height of Percent of Rep. a.i./100 kgTreated Plant in Control Height No. seed) Formulation cm (10 DAP) (10DAP) 3-1 1 ALTO 005LS 7.88 74.4 3-2 4 ALTO 005LS 5.33 50.4 3-3 8 ALTO005LS 2.75 26.0 3-4 16 ALTO 005LS 0.83 7.8 3-5 1 25 10.95 103.7 3-6 4 2510.25 97.0 3-7 8 25 9.88 93.5 3-8 16 25 9.20 87.1 3-9 1 26 9.67 91.73-10 4 26 9.00 85.2 3-11 8 26 9.68 91.5 3-12 16 26 8.70 82.3 3-13 1 888.25 78.1 3-14 4 88 6.75 63.9 3-15 8 88 5.55 52.7 3-16 16 88 4.3 40.83-17 1 89 7.85 74.3 3-18 4 89 6.25 59.2 3-19 8 89 4.93 46.6 3-20 16 893.68 34.8 3-21 1 90 8.43 79.6 3-22 4 90 6.53 61.8 3-23 8 90 5.00 47.33-24 16 90 3.68 34.8 3-25 1 91 7.85 74.3 3-26 4 91 6.60 62.4 3-27 8 915.15 48.7 3-28 16 91 3.40 32.2 3-29 0 Control 10.58 100.0 (Caldwell96(B-H52))

Example 10

Following the general procedure of Example 1, matrix particlesuspensions having the following compositions were produced. Weight % ofIngredients Formulation Ingredients 27 28 Cyproconazole* 3.00 3.00Chronopol 95 10.92 6.12 Polystyrene 1.20 6.00 Methocel A15LV 1.56 1.61Water 83.32 83.27 Total 100.00 100.00*100% a.i. basis. Compensate for purity with polymer.

The suspensions produced in this Example were applied to wheat using theprocedure set forth in Example 7. The table below shows and FIG. 4illustrates the safety of these treatments at 11 days after planting ascompared to Alto 005LS. Height of Percent of Rate (g Treated Controla.i./100 kg Plant in cm Height (11 Rep. No. seed) Formulation (11 DAP)DAP) 4-1 1 51 8.4 72.6 4-2 4 51 7.0 60.6 4-3 8 51 6.7 57.4 4-4 16 51 4.841.6 4-5 1 47 9.5 82.1 4-6 4 47 7.7 66.4 4-7 8 47 6.1 52.2 4-8 16 47 3.832.8 4-9 1 48 9.7 83.2 4-10 4 48 8.5 73.1 4-11 8 48 6.8 58.9 4-12 16 485.5 47.4 4-13 1 ALTO 005LS 9.1 78.2 4-14 4 ALTO 005LS 7.3 63.1 4-15 8ALTO 005LS 5.5 47.0 4-16 16 ALTO 005LS 3.0 25.9 4-17 1 5932801A2 10.892.9 4-18 4 5932801A2 9.7 83.9 4-19 8 5932801A2 9.3 80.0 4-20 165932801A2 8.6 74.1 4-21 1 5932801B2 10.8 93.1 4-22 4 5932801B2 10.1 86.94-23 8 5932801B2 8.9 77.0 4-24 16 5932801B2 8.6 73.9 4-25 0 Control (96Caldwell 11.6 100.0 (B-H52))

Example 11

Following the general procedure of Example 1, matrix particlesuspensions having the following compositions were produced. Weight % ofIngredients Formulation Ingredients 29 30 93 Cyproconazole* 20.1 3.043.71 Chronopol 95 79.9 10.41 8.67 Methocel A15LV — 1.27 1.09 Water —85.28 86.53 Total 100.0 100.0 100.0*100% a.i. basis. Compensate for purity with polymer.

The following procedure was used to prepare a matrix particle suspensionhaving the composition in the table below. A 38.5% by weight a.i.suspension of cyproconazole was prepared using a laboratory mill. Theparticles were milled to an average size of less than 10 microns indiameter. Separately, a solution was prepared containing 3.82% by weightof alginic acid and 0.15% by weight of calcium acetate in water. Thecyproconazole solution was warmed to 50 C with stirring. The alginicacid/calcium acetate was warmed to 60 C with stirring. The cyproconazolesuspension was poured rapidly into the stirring alginic acid solution.The resultant mixture was stirred until it equilibrated to roomtemparature (about 2 hours). The mixture was poured through a #50 meshsieve and bottled. Weight % of Ingredients Formulation Ingredients 82Cyproconazole* 14.05 Morwet D-425 1.83 Calcium Acetate 0.10 Alginic Acid2.42 Water 81.60 Total 100.0*100% a.i. basis. Compensate for purity with polymer.

The suspensions produced in this Example were applied to wheat using theprocedure set forth in Example 7. The table below shows and FIG. 5illustrates the safety of Formulation 29 at 10 days after planting (DAP)as compared to Alto 005LS.

Data Corresponding to FIG. 5

Height of Percent of Rate (g Treated Control a.i./100 kg Plant in cmHeight (10 Rep. No. Formulation seed) (10 DAP) DAP) 5-1 ALTO 005LS 18.08 79.1 5-2 ALTO 005LS 2 7.33 71.6 5-3 ALTO 005LS 4 5.63 55.0 5-4 ALTO005LS 8 4.15 40.5 5-5 29 1 8.13 79.5 5-6 29 2 8.38 81.9 5-7 29 4 8.1079.3 5-8 29 8 8.80 86.1 5-9 35 1 10.50 102.7 5-10 35 2 9.43 92.2 5-11 354 8.95 87.6 5-12 35 8 8.08 79.0 5-13 Untreated Check 0 10.23 100.0

The table below shows and FIG. 6 illustrates the safety of Formulation30 at 10 days after planting (DAP) as compared to Alto 005LS.

Data Corresponding to FIG. 6

Intended Height of Application Analytical Predicted Treated Percent ofRate (g a.i./ Percent Rate (g Plant in Control 100 kg Recovery ofa.i./100 kg cm (10 Height (10 Rep. No. Formulation seed) Applied seed)DAP) DAP) 6-1  97 1.1 69 0.76 8.63 79.63 6-2  97 4.4 81.4 3.58 7.0565.02 6-3  97 8.8 83 7.30 5.68 52.33 6-4  97 17.6 79.7 14.03 3.98 36.856-5  49 1.1 19.1 0.21 10.73 98.80 6-6  49 4.4 13.1 0.58 10.03 92.48 6-7 49 8.8 11.6 1.02 9.80 90.33 6-8  49 17.6 19 3.34 9.08 83.70 6-9  30 1.132.7 0.36 10.25 94.40 6-10 30 4.4 22.6 0.99 8.60 79.40 6-11 30 8.8 21.51.89 8.45 78.03 6-12 30 17.6 19.5 3.43 8.33 76.70 6-13 31 1.1 100.9 1.119.93 91.35 6-14 31 4.4 87.3 3.84 8.80 81.30 6-15 31 8.8 134.9 11.87 8.5378.63 6-16 31 17.6 116.9 20.57 7.23 66.53 6-17 93 1.1 79.1 0.87 8.5578.65 6-18 93 4.4 73.2 3.22 7.25 67.18 6-19 93 8.8 56.9 5.01 6.40 59.086-20 93 17.6 46.6 8.20 6.60 61.03 6-25 1 1.1 47.3 0.52 9.80 90.40 6-26 14.4 42.5 1.87 8.70 80.23 6-27 1 8.8 54.4 4.79 7.95 73.38 6-28 1 17.648.8 8.59 7.38 67.70 6-29 82 1.1 86.4 0.95 7.90 73.05 6-30 82 4.4 80.73.55 6.95 64.18 6-31 82 8.8 78.4 6.90 5.15 47.08 6-32 82 17.6 54 9.505.08 46.40 6-33 ALTO 1.1 122.7 1.35 8.05 74.30 005LS 6-34 ALTO 4.4 90.23.97 6.23 57.45 005LS 6-35 ALTO 8.8 95.6 8.41 3.83 35.50 005LS 6-36 ALTO17.6 89.2 15.70 2.18 20.10 005LS 6-37 Untreated 0 0.00 10.88 100.00Check

Example 12

Following the general procedure of Example 1, matrix particlesuspensions having the following compositions were produced. Weight % ofIngredients Formulation Ingredients 30 31 32 Cyproconazole* 3.04 22.3 30Chronopol 95 10.41 77.7 70 Methocel A15LV 1.27 Water 85.28 Total 100100.0 100*100% a.i. basis. Compensate for purity with polymer.

The suspensions produced in this Example were applied to wheat using theprocedure set forth in Example 7. The data in the table below show andFIG. 7 illustrates the safety of Formulation 30 and Formulation 31 at 10days after planting as compared to Alto 005LS. Intended Height ofApplication Analytical Predicted Treated Percent of Rate (g a.i./Percent Rate (g Plant in Control 100 kg Recovery of a.i./100 kg cm (10Height (10 Rep. No. Formulation seed) Applied seed) DAP) DAP) 6-1  971.1 69 0.76 8.63 79.63 6-2  97 4.4 81.4 3.58 7.05 65.02 6-3  97 8.8 837.30 5.68 52.33 6-4  97 17.6 79.7 14.03 3.98 36.85 6-5  49 1.1 19.1 0.2110.73 98.80 6-6  49 4.4 13.1 0.58 10.03 92.48 6-7  49 8.8 11.6 1.02 9.8090.33 6-8  49 17.6 19 3.34 9.08 83.70 6-9  30 1.1 32.7 0.36 10.25 94.406-10 30 4.4 22.6 0.99 8.60 79.40 6-11 30 8.8 21.5 1.89 8.45 78.03 6-1230 17.6 19.5 3.43 8.33 76.70 6-13 31 1.1 100.9 1.11 9.93 91.35 6-14 314.4 87.3 3.84 8.80 81.30 6-15 31 8.8 134.9 11.87 8.53 78.63 6-16 31 17.6116.9 20.57 7.23 66.53 6-17 93 1.1 79.1 0.87 8.55 78.65 6-18 93 4.4 73.23.22 7.25 67.18 6-19 93 8.8 56.9 5.01 6.40 59.08 6-20 93 17.6 46.6 8.206.60 61.03 6-25 1 1.1 47.3 0.52 9.80 90.40 6-26 1 4.4 42.5 1.87 8.7080.23 6-27 1 8.8 54.4 4.79 7.95 73.38 6-28 1 17.6 48.8 8.59 7.38 67.706-29 82 1.1 86.4 0.95 7.90 73.05 6-30 82 4.4 80.7 3.55 6.95 64.18 6-3182 8.8 78.4 6.90 5.15 47.08 6-32 82 17.6 54 9.50 5.08 46.40 6-33 ALTO1.1 122.7 1.35 8.05 74.30 005LS 6-34 ALTO 4.4 90.2 3.97 6.23 57.45 005LS6-35 ALTO 8.8 95.6 8.41 3.83 35.50 005LS 6-36 ALTO 17.6 89.2 15.70 2.1820.10 005LS 6-37 Untreated 0 0.00 10.88 100.00 Check

The table below show and FIG. 8 illustrates the safety of Formulation 31and Formulation 32 at 10 days after planting as compared to Alto 005LS.Percent of Rate (g Height of Control a.i./100 kg Treated Plant in Height(10 Rep. No. Formulation seed) cm (10 DAP) DAP) 8-1 ALTO 005LS 1 8.6388.6 8-2 ALTO 005LS 2 8.25 84.7 8-3 ALTO 005LS 4 7.43 76.3 8-4 ALTO005LS 8 6.38 65.6 8-5 31 1 9.50 97.8 8-6 31 2 8.90 91.4 8-7 31 4 9.3896.3 8-8 31 8 9.88 101.4 8-9 32 1 9.95 102.2 8-10 32 2 9.75 100.2 8-1132 4 9.75 100.2 8-12 32 8 10.15 104.3 8-13 Untreated 0 9.75 100 Check

Example 13

Following the general procedure of Example 1 and using the ingredientswhich are listed below matrix particle suspensions having the followingcompositions were produced. Biopol D400G was obtained from MonsantoCompany (St. Louis, Mo.). Polyvinylpyrollidone/vinyl acetate copolymer(PVP/VA S-630), which was used as a dispersant, was obtained from GAFChemicals Corp. (Wayne, N.J.). Weight % of Ingredients FormulationIngredients 33 34 35 Cyproconazole* 10 22.3 22.3 Biopol D400G — 77.7 —Chronopol 95 + inerts 90 — 77.7** Total 100 100.0 100.0*100% a.i. basis. Compensate for purity with polymer and inerts.

The suspensions produced in this Example were applied to wheat using theprocedure set forth in Example 7. The data in the table below show andFIG. 9 illustrates the safety of Formulation 33 and Formulation 34 at 10days after planting as compared to Alto 005LS. Height of Treated Percentof Rep. Rate (g a.i./ Plant in cm (10 Control Height No. Formulation 100kg seed) DAP) (10 DAP) 9-1 ALTO 1 8.63 88.6 005LS 9-2 ALTO 2 8.25 84.7005LS 9-3 ALTO 4 7.43 76.3 005LS 9-4 ALTO 8 6.38 65.6 005LS 9-5 33 19.50 97.5 9-6 33 2 9.63 98.9 9-7 33 4 9.38 96.3 9-8 33 8 8.75 90 9-9 341 10.25 105.4 9-10 34 2 8.50 87.3 9-11 34 4 8.63 88.6 9-12 34 8 10.05103.1 9-13 Untreated 0 9.75 100 Check

The data in the table below show and FIG. 10 illustrates the safety ofFormulation 35 at 10 days after planting as compared to Alto 005LS.Height of Treated Percent of Rep. Rate (g a.i./ Plant in cm (10 ControlHeight No. Formulation 100 kg seed) DAP) (10 DAP) 5-1 ALTO 005LS 1 8.0879.1 5-2 ALTO 005LS 2 7.33 71.6 5-3 ALTO 005LS 4 5.63 55.0 5-4 ALTO005LS 8 4.15 40.5 5-5 29 1 8.13 79.5 5-6 29 2 8.38 81.9 5-7 29 4 8.1079.3 5-8 29 8 8.80 86.1 5-9 35 1 10.50 102.7 5-10 35 2 9.43 92.2 5-11 354 8.95 87.6 5-12 35 8 8.08 79.0 5-13 Untreated 0 10.23 100.0 Check

Example 14

Following the general procedure of Example 1 matrix particle suspensionshaving the following compositions were produced. Weight % of IngredientsFormulation Ingredients 36 37 38 Cyproconazole *3.17 *3.01 *3.01 Elvanol51-05 1.64 1.26 1.26 Methocel A15LV — — — Chronopol 50 11.06 — —Chronopol 95 — 10.43 — Chronopol 100 — — 10.43 Water 84.13 85.30 85.30Total 100.00 100.00 100.00

The suspensions produced in this Example were applied to wheat using theprocedure set forth in Example 7. The data in the table below show andFIG. 11 illustrates the safety of these suspensions at 10 days afterplanting as compared to Alto 005LS. Height of Rate (g Treated Rep.a.i./100 kg Plant in cm Percent of Control No. Formulation seed) (10DAP) Height (10 DAP) 11-1 ALTO 005LS 1 10.75 78.2 11-2 ALTO 005LS 2 8.8864.5 11-3 ALTO 005LS 4 8.25 60.0 11-4 ALTO 005LS 8 6.38 46.4 11-5 38 112.75 92.7 11-6 38 2 12.25 89.1 11-7 38 4 10.88 79.1 11-8 38 8 9.88 71.811-9 36 1 12.13 88.2 11-10 36 2 12.13 88.2 11-11 36 4 11.25 81.8 11-1236 8 9.75 70.9 11-13 40 1 12.25 89.1 11-14 40 2 11.00 80.0 11-15 40 49.88 71.8 11-16 40 8 9.00 65.5 11-17 39 1 11.63 84.5 11-18 39 2 11.8886.4 11-19 39 4 11.00 80.0 11-20 39 8 10.00 72.7 11-21 30 1 13.50 98.211-22 30 2 12.88 93.6 11-23 30 4 12.38 90.0 11-24 30 8 10.50 76.4 11-2537 1 13.13 95.5 11-26 37 2 13.13 95.5 11-27 37 4 11.75 85.5 11-28 37 810.50 76.4 11-29 Untreated 0 13.75 100.0 Check

Example 15

Following the general procedure of Example 1 and using the ingredientswhich are listed below matrix particle suspensions having the followingcompositions were produced. Weight % of Ingredients FormulationIngredients 39 30 40 Cyproconazole* 3.05 3.04 3.04 Elvanol 51-05 — — —Methocel AI5LV 1.25 1.27 1.27 Chronopol 50 10.40 — — Chronopol 95 —10.41 — Chronopol 100 — — 10.41 Water 85.30 85.28 85.28 Total 100.00100.00 100.00*100% a.i. basis. Compensate for purity with polymer and inerts.

The suspensions produced in this Example were applied to wheat using theprocedure set forth in Example 7. The data in the table below show andFIG. 12 illustrates the safety of these compounds at 10 days afterplanting as compared to Alto 005LS. Height of Percent of Rate (g a.i./Treated Plant Control 100 kg in cm (10 Height (10 Rep. No. Formulationseed) DAP) DAP) 11-1 ALTO 1 10.75 78.2 005LS 11-2 ALTO 2 8.88 64.5 005LS11-3 ALTO 4 8.25 60.0 005LS 11-4 ALTO 8 6.38 46.4 005LS 11-5 38 1 12.7592.7 11-6 38 2 12.25 89.1 11-7 38 4 10.88 79.1 11-8 38 8 9.88 71.8 11-936 1 12.13 88.2 11-10 36 2 12.13 88.2 11-11 36 4 11.25 81.8 11-12 36 89.75 70.9 11-13 40 1 12.25 89.1 11-14 40 2 11.00 80.0 11-15 40 4 9.8871.8 11-16 40 8 9.00 65.5 11-17 39 1 11.63 84.5 11-18 39 2 11.88 86.411-19 39 4 11.00 80.0 11-20 39 8 10.00 72.7 11-21 30 1 13.50 98.2 11-2230 2 12.88 93.6 11-23 30 4 12.38 90.0 11-24 30 8 10.50 76.4 11-25 37 113.13 95.5 11-26 37 2 13.13 95.5 11-27 37 4 11.75 85.5 11-28 37 8 10.5076.4 11-29 Untreated 0 13.75 100.0 Check

Example 16

Following the general procedure of Example 2 matrix particle suspensionshaving the following compositions were produced. Lucite #29 was obtainedfrom Polysciences Inc. (Warrington, Pa.). Weight % of IngredientsFormulation Ingredients 41 42 Cyproconazole* 2.95 1.48 Lucite #29 11.80— Cellulose acetate — 13.27 butyrate Methocel A15LV 1.00 1.00 Water84.25 84.25 Total 100.00 100.00*100% a.i. basis. Compensate for purity with polymer.

The suspensions produced in this Example were applied to wheat using theprocedure set forth in Example 7. The data in the table below show andFIG. 13 illustrates the safety of these compounds at 10 days afterplanting as compared to Alto 005LS. Analytical Avg. No. Height ofPercent Predicted of Plants Treated % of Rate (g Recovery Rate (gGerminating Plant in Control a.i./100 kg of a.i./100 kg (out cm (9Height (9 Rep. No. Formulation seed) Applied seed) of 12) DAP) DAP)13-1  ALTO 4.4 98.4 4.3 11.25 8.5 73.7 005LS 13-2  ALTO 8.8 93.1 8.2 7.55.6 48 005LS 13-3  ALTO 17.6 90.5 15.9 3.25 5. 42.6 005LS 13-8  42 4.438.2 1.85 10.25 11.3 97.6 13-9  42 8.8 61.9 5.99 11.25 10.2 88 13-10 4217.6 72.8 14.09 11.25 9.4 81.2 13-11 42 35.2 81.6 31.6 11.75 8.9 76.913-16 41 4.4 68.4 3.31 10.25 11. 94.6 13-17 41 8.8 77.7 7.52 11.5 10.86.2 13-18 41 17.6 83.9 16.24 11 10. 86.3 13-19 41 35.2 91.4 35.39 11.758.8 75.4 13-20 24 4.4 123.2 5.96 11.5 10.1 86.6 13-21 24 8.8 120.9 11.78.25 8.4 72.1 13-22 24 17.6 111.9 21.66 9.75 9.5 82.1 13-23 24 35.2138.6 53.67 11.25 8.7 74.6 13-24 UNTREATED 0 12 11.6 100 CHECK

Example 17

Following the general procedure of Example 2, a matrix particlesuspension having the following composition and properties was produced.Tebuconazole was obtained from Bayer (Leverkusen, Germany). Formulation43 % w/w Ingredients Tebuconazole* 3.52 Chronopol 95 14.35 Urea 4.49Methocel A15LV 0.50 Water 77.14 Total 100.0 Property Tebuconazole* (Wt%) 3.37 Density, g/mL, 24° C. 1.05 Mean particle size, μm 41*100% a.i. basis. Compensate for purity with polymer.

Example 18

Following the general procedure of Example 1 a matrix particlesuspension having the following composition and properties was produced.Formulation 44 % w/w Ingredients Tebuconazole* 2.95 Lucite # 29 11.80Methocel A15LV 1.00 Water 84.25 Total 100.0 Property % Tebuconazole 3.34Density, g/cc, 24° C. 1.03 Particle Size, microns, 1.9 mean*100% a.i. basis. Compensate for purity with polymer.

Formulation 43 and Formulation 44 were applied to wheat using theprocedure set forth in Example 7. The data in the table below show andFIG. 14 illustrates the safety of these compounds at 10 days afterplanting as compared to Raxil (Bayer, Leverkusen, Germany), a commercialfast-release formulation of tebuconazole. Analytical Avg. No. Height ofPercent Predicted of Plants Treated % of Rate (g Recovery Rate (gGerminating Plant in Control a.i./100 kg of a.i./100 kg (out cm (11Height Rep. No. Formulation seed) Applied seed) of 12) DAP) (11 DAP)14-1  ALTO 8.8 85.2 7.5 11.8 6.3 56.4 005LS 14-2  RAXIL 8.8 88.3 7.812.0 8.1 72.1 0.26 FS 14-3  OPUS 8.8 62.4 5.5 12.0 2.9 25.5 125 SC 14-4 41 8.8 66.3 5.8 12.0 10.2 91.4 14-5  41 17.6 86.4 15.2 12.0 9.6 85.914-6  41 35.2 96.8 34.1 12.0 8.7 77.5 14-7  15 8.8 75.3 6.6 11.8 9.686.0 14-8  15 17.6 82 14.4 12.0 9.3 83.1 14-9  15 35.2 94.4 33.2 12.09.1 81.3 14-10 77 8.8 88.8 7.8 12.0 9.4 84.1 14-11 77 17.6 78.4 13.812.0 8.3 73.9 14-12 77 35.2 100.3 35.3 11.8 7.9 70.2 14-13 43 8.8 73.16.4 12.0 10.5 93.9 14-14 43 17.6 80.8 14.2 12.0 9.9 88.3 14-15 43 35.295.5 33.6 12.0 9.5 84.8 14-16 44 8.8 94.7 8.3 12.0 9.7 86.4 14-17 4417.6 69.6 12.2 11.5 9.9 88.3 14-18 44 35.2 104.3 36.7 12.0 9.0 80.514-19 45 8.8 64 5.6 12.0 6.3 56.3 14-20 45 17.6 63.9 11.2 12.0 4.2 37.514-21 45 35.2 84.5 29.7 12.0 2.5 21.9 14-22 46 8.8 78.9 6.9 11.5 7.869.5 14-23 46 17.6 77.7 13.7 12.0 6.7 59.5 14-24 46 35.2 93.2 32.8 12.03.7 33.1 14-25 UNTREATED 0 0 0.0 12.0 11.2 100.0 CHECK

Example 19

Following the general procedure of Example 2 a matrix particlesuspension having the following composition and properties was produced.Formulation 45 % w/w Ingredients Epoxiconazole* 2.95 Chronopol 95 11.80Methocel A15LV 1.00 Water 84.25 Total 100.00 Property Epoxiconazole*3.01 (Wt %) Density, g/mL, 24° C. 1.04 Ave. particle size, μm 2.80*100% a.i. basis. Compensate for purity with polymer.

Example 20

Following the general procedure of Example 2 a matrix particlesuspension having the following composition and properties was produced.Formulation 46 % w/w Ingredients Epoxiconazole* 2.95 Lucite #29 11.80Methocel Al5LV 1.00 Water 84.25 Total 100.00 Property Epoxiconazole*3.18 (Wt %) Density, g/cc, 24° C. — Particle Size, microns, — mean*100% a.i. basis. Compensate for purity with polymer.

The Formulation 43 and Formulation 44 suspensions were applied to wheatusing the procedure set forth in Example 7. The data in the table belowshow and FIG. 15 illustrates the effects of these suspensions werecompared with the effect of Opus (BASF AG, Limburgerhof, Germany), acommercial fast-release formulation of epoxiconazole. The maximum saferate of application of Opus as a seed treatment is approximately 1 g/100kg seed. Analytical Avg. No. Height of Percent Predicted of PlantsTreated % of Rate (g Recovery Rate (g Germinating Plant in Controla.i./100 kg of a.i./100 kg (out cm (11 Height Rep. No. Formulation seed)Applied seed) of 12) DAP) (11 DAP) 14-1  ALTO 8.8 85.2 7.5 11.8 6.3 56.4005LS 14-2  RAXIL 8.8 88.3 7.8 12.0 8.1 72.1 0.26 FS 14-3  OPUS 8.8 62.45.5 12.0 2.9 25.5 125 SC 14-4  41 8.8 66.3 5.8 12.0 10.2 91.4 14-5  4117.6 86.4 15.2 12.0 9.6 85.9 14-6  41 35.2 96.8 34.1 12.0 8.7 77.5 14-7 15 8.8 75.3 6.6 11.8 9.6 86.0 14-8  15 17.6 82 14.4 12.0 9.3 83.1 14-9 15 35.2 94.4 33.2 12.0 9.1 81.3 14-10 77 8.8 88.8 7.8 12.0 9.4 84.114-11 77 17.6 78.4 13.8 12.0 8.3 73.9 14-12 77 35.2 100.3 35.3 11.8 7.970.2 14-13 43 8.8 73.1 6.4 12.0 10.5 93.9 14-14 43 17.6 80.8 14.2 12.09.9 88.3 14-15 43 35.2 95.5 33.6 12.0 9.5 84.8 14-16 44 8.8 94.7 8.312.0 9.7 86.4 14-17 44 17.6 69.6 12.2 11.5 9.9 88.3 14-18 44 35.2 104.336.7 12.0 9.0 80.5 14-19 45 8.8 64 5.6 12.0 6.3 56.3 14-20 45 17.6 63.911.2 12.0 4.2 37.5 14-21 45 35.2 84.5 29.7 12.0 2.5 21.9 14-22 46 8.878.9 6.9 11.5 7.8 69.5 14-23 46 17.6 77.7 13.7 12.0 6.7 59.5 14-24 4635.2 93.2 32.8 12.0 3.7 33.1 14-25 UNTREATED 0 0 0.0 12.0 11.2 100.0CHECK

Wheat seeds were coated with an aqueous suspension of the matrixparticles of the present invention using the following procedure.

The following water-based film coating concentrates were used for thefilm coating of seeds: Blue Opacoat-AG (Colorcon, West Point, Pa.),Sepiret 8127 Rouge (Seppic, Paris, France), and Sepiret 2020 A Rouge(Seppie, Paris, France). Sepiret and Opacoat formulas are ready-to-usecolored film-forming compositions designed for the application of thinfilms of biodegradable polymers, usually cellulose derivatives ofnatural origin.

A batch film coating system (Coating Machinery Systems (CMS) PSC-5,Ames, Iowa) was used to apply a precision coating to specific amounts ofseed. The water-based film coating concentrates were usually diluted toa 15% w/w solids concentration with water before application. Particleformulations were usually diluted to an active ingredient concentrationof 0.12% w/w and coated on seed as a separate coating (using theprocedure of Example 7) or in combination with the water-based filmcoatings. Drying temperatures were usually inlet/outlet at 100° F./90°F. with air flows at 300 cubic feet per minute (CFM). Added coatingweights were usually calculated at about 2% wlw, which provides foruniform coverage. After coating, the individual coated batches of seedwere analyzed for cyproconazole content (“found a.i.”). Formulation: 4748 49 50 Treatment: T1 T2 T3 T4 Wheat seed Q.S. Q.S. Q.S. Q.S.Cyproconazole @ 176, 88, 176, 88, 176, 88, 176, 88, 100% (ppm) 44, 1144, 11 44, 11 44, 11 Found a.i. (ppm) 139, 63, 120, 50, 29, — 18, —

Formulation: 51 Alto 05LS Treatment: T5 Wheat seed Q.S. Q.S. Q.S.Cyproconazole 176, 88, 44, 176, 88, 44, 176, 88, @100% (ppm) 11 22, 1144, 22, 11 Found a.i., ppm (2) 156, 77, 36, — 127, 71, 32, 129, 52, 16,8 27, 14, —Q.S. = Quantity Sufficient to dilute to the required concentration.

Formulation: 29 29 29 61 Treatment: T6 T7 T8 T9 Wheat seed Q.S. Q.S.Q.S. Q.S. Methocel A15LV 110 ppm — 100 ppm Urea — 890 ppm — — AmmoniumSulfate — — 890 ppm Cyproconazole 88, 44, 22, 88, 44, 22, 88, 44, 22,88, 44, 22, @100% (ppm) 11 11 11 11 Found a.i., ppm (1) 43, 25, 15, —51, 17, 10, —

Formulation: 30 Treatment: T10 Wheat seed Q.S. Methocel Al5LV —Cyproconazole 88, 44, 22, 11 @100% (ppm) Found a.i., ppm (1) 33, 25, 9,—Q.S. = Quantity Sufficient to dilute to the required concentration.

The data in the table below show and FIG. 16 illustrates the safety ofthe suspensions at an application rate of 16 g active ingredient per 100kg seed, as compared with Alto 005LS. Avg. No. Rate of Plants Height of% of (g a.i./ Germinating Treated Control 100 kg (out of Plant in cmHeight (8 Rep. No. Treatment seed) 12) (8 DAP) DAP) 16-1  Untreated 012.0 11.6 100.0 Check 16-2  T1 1 11.8 9.5 82.1 16-3  T2 1 12.0 9.7 83.216-4  T3 1 11.5 10.8 92.9 16-5  T4 1 12.0 10.8 93.1 16-6  T5 1 12.0 8.472.6 16-7  ALTO 1 12.0 9.1 78.2 005LS 16-9  T1 4 11.8 7.7 66.4 16-10 T24 11.8 8.5 73.1 16-11 T3 4 11.5 9.7 83.9 16-12 T4 4 12.0 10.1 86.9 16-13T5 4 12.0 7.0 60.6 16-14 ALTO 4 12.0 7.3 63.1 005LS 16-16 T1 8 11.5 6.152.2 16-17 T2 8 12.0 6.8 58.9 16-18 T3 8 12.0 9.3 80.0 16-19 T4 8 12.08.9 77.0 16-20 T5 8 12.0 6.7 57.4 16-21 ALTO 8 11.8 5.5 47.0 005LS 16-23T1 16 12.0 3.8 32.8 16-24 T2 16 12.0 5.5 47.4 16-25 T3 16 11.8 8.6 74.116-26 T4 16 12.0 8.6 73.9 16-27 T5 16 12.0 4.8 41.6 16-28 ALTO 16 11.83.0 25.9 005LS

Example 22

In this example, the polymers used were poly(methyl methacrylate)(350,000 MW, Polysciences, Inc., Warrington, Pa.) or poly(styrene/maleicanhydride) (75% styrene, Sigma Chemical Co., St. Louis, Mo.). Theorganic solvent was methylene chloride (American Chemical Societyanalytical reagent grade). Dispersing agents used were Methocel A15LV(methyl cellulose, Dow Chemical, Midland, Mich.); Elvanol 51-05(polyvinyl alcohol, DuPont, Wilmington, Del.); or Yelkinol P (lecithin,Archer Daniels Midland Company, Decatur Ill.). Active ingredients usedwere epoxiconazole (technical grade @ 96.2%, BASF) or tebuconazole(technical grade @ 98.6%, Bayer).

All formulations were prepared by an oil-in-water (O/W) emulsion/solventevaporation procedure. Briefly, the polymer and active ingredient weredissolved in methylene chloride at room temperature to form ahydrophobic solution (15% solids). The hydrophobic (oil, O) phase wasadded to a cooled (<5° C.) 0.5-3.0% aqueous dispersant solution (water,W) and sheared with a Silverson Model L4R homogenizer (large holescreen, 1.5 cm.) for 5 minutes at setting #5 to form an emulsion. Theorganic solvent was then evaporated with stirring at ambienttemperatures in a fume hood. The resulting particle preparations werenormally passed through a #60 mesh sieve to remove large particles.These particles were examined microscopically with a Leitz Dialux 20EBmicroscope to check for crystals and particle morphology, and evaluatedusing a Coulter LS-130 particle size analyzer to determine averageparticle size and the number of modes in the distribution.

To assay the rate of release of active ingredient from particleformulations, an aliquot of a formulation was placed in a glass bottleat a concentration at which a released active ingredient was expected tobe <½ the water solubility level. A solvent was then added (water or 10%acetone). At various intervals, the bottle was shaken (200 times at time0, 20 times for other intervals). An aliquot was removed, centrifuged 15minutes at 2700 rpm, and filtered through a 0.45 micron PTFE filter(after discarding the first 2 mL). Assays for epoxiconazole andtebuconazole were then carried out by HPLC.

Particle suspensions having the following compositions were produced.

Epoxiconazole-Containing Matrix Particle Formulations—Composition (%,w/w)

Weight % of Ingredients Formulation Ingredients 52 53 54 Epoxiconazole 3.00  3.00  3.00 (100% a.i. basis) Polymer 27.00 (a)  12.00 (b)  12.00(b) Methocel A15LV — —  2.00 Elvanol 51-05  4.00 — — Yelkinol P —  1.50— Water  83.50  83.50  83.00 Total 100.00 100.00 100.00 Evaluation DataFormulation 52 53 54 Loading of a.i. 10% 20% 20% (% w/w) O/W ratio in1/5 3/2 3/2 emulsion Ave. particle size, 11.35 μm, 1.37 μm, 3.04 μm,mode: trimodal bimodal bimodal Init. % a.i./ 3.57/0.18 3.44/1.003.94/0.2 % REA*Polymers: (a) Poly(methylmethacrylate), (b) Poly(styrene/maleicanhydride)*REA = Readily Extractable Active.

Tebuconazole-Containing Matrix Particle Formulations—Composition (%,w/w)

Weight % of Ingredients Formulation Ingredients 55 56 57 Tebuconazole3.00 4.50 6.00 (100% a.i. basis) Polymer* 12.00 (a) 10.50 (a) 9.00 (a)Methocel A15LV 1.00 1.00 1.00 Water 84.00 84.00 84.00 Total 100.00100.00 100.00 Evaluation Data Formulation 52 53 54 Loading of a.i., % 2030 40 O/W Ratio in 3/2 3/2 3/2 emulsion Ave. particle size, 9.14 μm,7.36 μm, 13.48 μm, mode: bimodal bimodal trimodal Init. % a.i./%3.25/0.68 4.92/2.01 5.75/2.21 REA:*(a) Poly(methylmethacrylate), (b) Poly(styrene/maleic anhydride)In addition, phytotoxicity of the formulations on wheat and theirrelease rates into water and into 10% acetone solutions were determined.This information is summarized below.

Epoxiconazole-Containing Matrix Particle Formulations—Phytotoxicity andRelease Rates

Formulation 58 53 54 % Release of epoxiconazole, after 269 hrs intowater 0.9 6.56 1.63 into 10% Acetone 9.71 46.7 26.6

Safety on Wheat* Formulation 58 53 54 25 g a.i./100 kg 96.9% 66.4% 92.2%seed (25.4 g) (12.4 g) (28.6 g) 50 g a.i./100 kg 91.8% 20.0% 75.4% seed(46.4 g) (42.2 g) (53.3 g) Opus, 8 g/100 kg 22.5%  (6.4 g) Control  100%(0 g a.i./100 kg)   (0 g)*Plant height as a % of the height of untreated control plants.Numbers in parenthesis are the grams of active ingredient found by assayto be on 100 kg of treated seed.

Tebuconazole-Containing Matrix Particle Formulations—Phytotoxicity andRelease Rates

Formulation 55 56 57 % Release, 269 hrs into water  2.53  3.79 14.5 into10% acetone 24.9 46.2 60.0 Safety on Wheat*  50 g/100 kg 89.7% 78.4%70.3% seed (47 g) (45 g) (49 g)  75 g/100 kg 83.8% 77.3% 68.7% seed (70g) (72 g) (78 g) 100 g/100 kg 78.4% 74.1% 60.8% seed (95 g) (92 g) (99g) Raxil, 25 g/100 kg 40.3% (26 g) Control (0 g/100 kg)  100%  (0 g)*% of height of untreated control.Numbers in parenthesis are the grams of active ingredient found by assayto be on 100 kg of treated seed.

Particles having the same polymer and active ingredient loading(Formulation 53 versus Formulation 54) but using a different dispersanthave much different release rates and corresponding differences insafety on wheat. The high release rate and higher initial % REA ofFormulation 53 gives a product having poor safety on wheat. However thesame loading in the same polymer processed with a different dispersantgives a recipe with a lower release rate and readily extractable active(REA) and higher safety on wheat. In addition, the rates of release ofactive ingredients are higher (and safety on wheat decreasescorrespondingly) as the loading in the particle is increased.

This study indicates that release rates can be changed by processing andactive ingredient loading (concentration) in the matrixed particle. Asactive ingredient concentration increases, release rates increaselikewise. Lower release rates tend to result in higher safety on wheat.When different dispersing agents are used for the preparation ofemulsions, the emulsion quality and the release rate of the resultingparticles are affected.

Poly(methylmethacrylate) and poly(styrene-maleic anhydride) are usefulpolymers for producing particles that increase the safety ofepoxiconazole and tebuconazole on wheat.

Example 23

For this Example, the polymer used was poly(styrene/maleic anhydride)(75% styrene, Sigma Chemical Co., St. Louis, Mo.). All organic solventswere of American Chemical Society (A.C.S.) analytical reagent grade. Thedispersing agent used was Methocel A15LV (methyl cellulose, DowChemical, Midland, Mich.). The active ingredients used were as follows:the fungicide triticonazole (technical grade @ 91.8%, Rhone-Poulenc AgCo., Research Triangle Park, N.C.), the herbicide triallate (technicalgrade @ 94%; Monsanto Company, St. Louis, Mo.), the Strobilurinfungicide MON 46100 (technical grade @ 95%; Monsanto Company, St. Louis,Mo.), the herbicide safener furilazole (MON 13900, technical grade @95%; Monsanto Company, St. Louis, Mo.); the insecticide chlorpyrifos(high purity grade @ 99%; Dow Chemical Co., Midland, Mich.); amorpholine-type fungicide, fenpropimorph (used “as is” in the form ofthe 750 g/L Corbel formulation, BASF AG, Limburgerhof, Germany); acarbamoyl imidazole-type fungicide, prochloraz (high purity grade @ 99%;Monsanto Company, St. Louis, Mo.).

Matrixed particle formulations were prepared by an oil-in-water (O/W)emulsion/solvent evaporation procedure. Briefly, the polymer and activeingredient used were dissolved in methylene chloride at room temperatureto form a 15% solids hydrophobic (oil, O) solution. This oil phase wasadded to a cooled (<5° C.) 0.5-3.0% aqueous dispersant solution (water,W) and sheared with a Silverson Model L4R homogenizer (large holescreen, 1.5 cm.) for 5 minutes at setting #5 to form an emulsion. Theorganic solvent was then evaporated with stirring at ambienttemperatures in a fume hood. The resulting formulations were normallypassed through a #60 mesh sieve to remove large particles and thenevaluated. The particles were subjected to microscopic examination witha Leitz Dialux 20EB microscope to check for crystals and particlemorphology and a particle-size evaluation using a Coulter LS-130particle size analyzer to determine the average particle size and numberof modes in the distribution.

Test compositions were prepared and their physical properties evaluated.The two recipes used are described below. Recipe B was necessary fortriticonazole because much crystal growth occurs when recipe A is used.Recipe A produces a 20% active ingredient loading for the particles andRecipe B produces a 5% loading.

Recipes (%, w/w)

Ingredients Recipe A Recipe B Active Ingredient 3.00 0.75Poly(styrene/maleic 12.00 14.25 anhydride) 75:25 Methocel A15LV 2.002.00 Water 83.00 83.00 Total 100.00 100.00

Particle size analyses were carried out on the Formulation 59 andfenpropimorph recipes and estimates from photographs were used for theother recipes. TABLE 6 Recipe References Ave. size Active IngredientFormulation Recipe (μm) Triticonazole 60 B ˜5 MON 46100 61 A 5.4Fenpropimorph 62 A 2.7 Furilazole 63 A ˜5 Triallate 64 A ˜5 Chlorpyrifos65 A ˜5 Prochloraz 66 A 4.8

Formulation 62 showed increased safety compared to Corbel, a commercialfast-release formulation of fenpropimorph, when applied as a seedtreatment to wheat at rates of 50-200 gm a.i./100 kg seed.

Example 24

Polymers used were poly(methyl methacrylate) (350,000 MW, Polysciences,Inc., Warrington, Pa.) and poly(styrene/maleic anhydride) (75% styrene,Sigma Chemical Co., St. Louis, Mo.) were used. All organic solvents wereof American Chemical Society (A.C.S.) analytical reagent grade.Dispersing agents used were Methocel A15LV (Dow Chemical, Midland,Mich.) and Elvanol 51-05 (polyvinyl alcohol, DuPont, Wilmington, Del.).

Particles were prepared by an oil-in-water (O/W) emulsion/solventevaporation procedure. Briefly, the polymer and active ingredient usedwere dissolved in methylene chloride at room temperature to form a 15%solids hydrophobic solution (oil phase, O). This oil phase was added toa cooled (<5° C.) 0.5-3.0% aqueous dispersant solution (aqueoussolution, W) and sheared with a Silverson Model L4R homogenizer (largehole screen, 1.5 cm.) for 5 minutes at setting #3 to form an emulsion.The solvent was then evaporated with stirring at ambient temperatures ina fume hood. Assays for active ingredient concentration were made andfurther evaporation of water was carried out to give the calculatedfinal concentration. The resulting particles were passed through a #60mesh sieve to remove large particles and then evaluated. Severalevaluations were made, including microscopic examination with a LeitzDialux 20EB microscope, pH, density, viscosity, and particle sizedistribution by Coulter LS-130 particle size analyzer.

Seed treatment formulations, their physical properties, andphytotoxicity data from greenhouse trials are described below.

Seed Treatment Formulations

Weight % of Ingredients Formulation Ingredients 67 68 69 70 71 72 73 74Epoxiconazole* 3.00 3.00 3.00 3.00 — — — — Tebuconazole* — — — — 10.0010.00 10.00 10.00 Polymer 27.00 (1) 12.00 (2) 27.00 (2) 12.00 (1) 40.00(2) 15.00 (2) 40.00 (1) 15.00 (1) Methyl Cellulose — 1.86 1.00 1.50 1.401.70 1.40 1.58 Polyvinyl Alcohol 3.85 — — — — — — — Water 66.15 83.1469.00 83.50 48.60 73.30 48.60 73.42 Total 100.00 100.00 100.00 100.00100.00 100.00 100.00 100.00*100% a.i. basis.Polymers: (1) poly(methylmethacrylate); (2), poly(styrene-maleicanhydride) copolymer 75:25 ratio.The table below provides information regarding physical properties ofthe particle preparations.

Physical Properties

Formulation Property 67 68 69 70 71 72 73 74 % a.i. 2.94 3.01 2.96 2.939.39 10.13 9.89 9.98 % REA 0.27 0.19 0.03 0.55 0.08 1.19 0.24 1.50 t°(C.) when 23.7 23.7 24.2 23.0 23.3 23.2 22.9 23.2 measured Density, g/mL1.07 1.03 1.05 1.03 1.08 1.05 1.10 1.05 Viscosity, 3.61 2.04 3.34 1.9719.0 4.46 25.9 4.21 60 rpm, cps pH 7.07 4.02 3.36 6.82 3.31 3.77 6.255.96

Phytotoxicity of Tebuconazole-Containing Formulations (% of ControlHeight)

g a.i./ 100 kg Formulation seed 71 72 73 74 75 Raxil 16 — — — — — 76.325 — — — — 95.5 — 50 82.1 69.8 89.7 70.3 89.6 — 75 84.5 64.4 83.8 68.7 —— 100 — — 78.4 60.8 — —LSD(.05) = 19.14

Phytotoxicity of Epoxiconazole-Containing Formulations (% of ControlHeight)

g a.i./ Formulation 100 kg MON MON MON MON MON seed 24531 24532 2453324534 24555 Opus 5 — — — — — 32.5 25 93.8 91.2 93.8 83.0 96.2 8.6 5083.4 73.3 98.0 43.3 90.5 — 75 77.9 61.4 86.8 24.3 87.9 —

Epoxiconazole-containing formulations showed much less phytotoxicitythan the commercial reference, Opus. Likewise, tebuconazole-containingformulations showed less phytotoxicity than the commercial reference,Raxil.

Formulation 75 and Formulation 76 were also tested as foliar treatmentsof soybean. At rates of 50 and 250 ppm active ingredient, soybean plantstreated with Formulation 75 and Formulation 76 as foliar treatmentsdisplayed substantially greater vigor than plants treated with Foliculurand Opus, particularly at the higher application rate.

The dispersant used for all of the formulations was Methocel a15LV, withthe exception of Formulation 67. This formulation showed betterprocessing with Elvanol 51-05 as a dispersant.

Example 25

We evaluated particle formulations containing cyproconazole for efficacyand duration in controlling brown leaf rust of wheat (caused by Pucciniarecondite) in greenhouse experiments. Wheat seed (cv. Fortuna) weretreated with test treatments (Formulation 42, Formulation 15, orFormulation 77, all at 32 g cyproconazole per 100 kg seed) and Alto005LS (at 1 g cyproconazole per 100 kg seed) and seeded in standard 4″square pots containing sterilized Dupo silt loam soil. Seeding was doneat a rate of 1 seed per pot, with four replicate pots of each treatmentrate. Seeds were covered with approximately 2 cm of the same soil andincubated under a 12 hour photoperiod, at 50% relative humidity. Growthroom temperatures were maintained at 16° C. during the 12 hour lightperiod and at 12° C. during the 12 hour dark period. Twenty days afterplanting, plants grown from treated seed were inoculated withurediospores of P. recondite. The inoculated plants were incubated for24 hours in a mist tent at 20° C. to allow for disease infection.Disease severity was evaluated 8-10 days after inoculation. The tablebelow and FIG. 17 show the percent of rust control in this experiment inplants inoculated 20 days after planting (second leaf stage). Diseaseseverity in untreated control plants was about 61.3%. We observed anincrease in the efficacy and duration of disease control by matrixparticle formulations, which permitted treatment of plants with a higherrate of the active ingredient than would be tolerated if the plants weretreated with a standard formulation such as Alto 005LS. % Rust ControlFormulation (2nd Leaf) 42 90 15 30 77 94 Alto 005LS 25

Example 26

Readily Extractable Active Ingredient (REA)

The following method can be used to estimate the amount of free activeoutside the particle of the present invention active plus the activeingredient immediately extractable with water from the particle of thepresent invention.

Transfer an aliquot of the formulation to glass bottle. Add water shake200 times. Immediately withdraw an aliquot of the shaken solution andfilter it through a 0.45 micron PTFE filter (discarding the first 3 mL).Assay by HPLC. The resulting raw ppm value in the tested aliquot must beless than half of the saturation concentration of the active ingredientassayed. If the raw ppm value is higher than half the saturationconcentration of the active ingredient, the procedure must be rerun withless formulation. For example, the water saturation concentration ofepoxiconazole is 7 ppm at room temperature. Therefore, the maximumresulting raw ppm value in a tested aliquot of an epoxiconazole shakensolution must be less than 3.5 ppm. The water saturation concentrationof tebuconazole is 32 ppm. Therefore, the maximum resulting raw ppmvalue in a tested aliquot of a tebuconazole shaken solution must be lessthan 16 ppm.

Example 27

Release Rate Assay—General Method

An aliquot of formulation is placed in a glass bottle at a concentrationwhere released triazole is expected to be <½ the water solubility level.Water is added so that the total volume is about 450 mL. The pH of themedium is maintained or adjusted using a phosphate buffer. At variousintervals the bottle is shaken (200 times at time 0, 20 times for otherintervals). An aliquot is removed, centrifuged 15 minutes at 2700 rpm,and filtered through a 0.45 micron PTFE filter (after discarding thefirst 2 mL). Assays for epoxiconazole and tebuconazole are then carriedout by HPLC. If the experiment calls for an adjustment of pH during thecourse of the experiment, the pH is adjusted using a phosphate bufferand an aliquot is immediately removed for assay.

Many changes and modifications of the invention described in thisspecification will occur to those skilled in the art upon studying theteachings of this specification. All such changes and modificationswhich are within the spirit of the present invention are intended to beincluded in the claims.

1-18. (canceled)
 19. A method of producing a particle wherein theparticle comprises a triazole fungicide in a polymer matrix, the methodcomprising: (a) providing a hydrophobic solution comprising a triazolefungicide, a polymer, and a solvent; (b) mixing the hydrophobic solutionand an aqueous medium to produce a dispersion of droplets of thehydrophobic solution in the aqueous medium; and (c) evaporating thesolvent from the dispersion to produce a particle comprising a triazolefungicide in a polymer matrix.
 20. The method of claim 19 wherein thetriazole fungicide comprises a compound selected from the groupconsisting of bitertanol, bromuconazole, cyproconazole, difenoconazole,epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol,hexaconazole, imibenconazole, metconazole, myclobutanil, penconazole,propiconazole, tebuconazole, tetraconazole, triadimefon, triadimenol,and triticonazole.
 21. The particle of claim 20 wherein the triazolefungicide comprises a compound selected from the group consisting ofcyproconazole, epoxiconazole, tebuconazole, triadimefon, andtriadimenol.
 22. The method of claim 20 wherein the triazole fungicidecomprises cyproconazole.
 23. The method of claim 20 wherein the triazolefungicide comprises tebuconazole.
 24. The method of claim 20 wherein thetriazole fungicide comprises epoxiconazole.
 25. The method of claim 20wherein the triazole fungicide comprises triadimenol.
 26. The method ofclaim 20 wherein the triazole fungicide comprises triadimefon.
 27. Themethod of claim 19 wherein the hydrophobic solution further comprises adispersing agent.
 28. The method of claim 19 wherein the aqueous mediumcomprises a dispersing agent.
 29. The method of claim 19 wherein thesolvent is a substantially hydrophobic solvent.
 30. The method of claim29 wherein the solvent comprises a compound selected from the groupconsisting of halogenated hydrocarbons, aromatic compounds,hydrocarbons, ethers, and esters.
 31. The method of claim 30 wherein thesolvent comprises a compound selected from the group consisting of ethylacetate, chloroform, carbon tetrachloride, acetonitrile, diethyl ether,dimethyl ether, acetone, methylethylketone, pentane, hexane, hexanes,heptane, dioxane, ethanol, methanol, pyridine, propanol, 2-propanol,butanol, 2-butanol, t-butyl alcohol, isobutyl alcohol,perchloroethylene, tetrachloroethane, o-xylene, m-xylene, p-xylene,toluene, benzene, mesitylene, chlorobenzene, o-dichlorobenzene,m-dichlorobenzene, and p-dichlorobenzene.
 32. The method of claim 31wherein the solvent comprises methylene chloride.
 33. The method ofclaim 19 wherein step (c) comprises applying a source of vacuum to thedispersion.
 34. The method of claim 19 wherein step (c) comprisesapplying heat to the dispersion.
 35. The method of claim 19 wherein step(c) comprises lyophilizing the dispersion. 36-45. (canceled)
 46. Themethod of claim 19, wherein the polymer matrix comprises a polymerselected from the group consisting of poly(methylmethacrylate),poly(lactic acid), a poly(lactic acid-glycolic acid) copolymer,cellulose acetate butyrate, a poly(styrene), hydroxybutyricacid-hydroxyvaleric acid copolymer, a styrene maleic anhydridecopolymer, poly(methylvinyl ether-maleic acid), poly(caprolactone),poly(n-amylmethacrylate), wood rosin, a polyanhydride, a polyorthoester,a poly(cyanoacrylate), poly(dioxanone), ethyl cellulose, a ethyl vinylacetate polymer, poly(ethylene glycol), poly(vinylpyrrolidone), anacetylated monogylceride, an acetylated digylceride, an acetylatedtrigylceride, poly(phosphazene), chlorinated natural rubber, a vinylpolymer, polyvinyl chloride, a hydroxyalkylcellulose, polybutadiene,polyurethane, a vinylidene chloride polymer, a styrene-butadienecopolymer, a styrene-acrylic copolymer, an alkylvinylether polymer, acellulose acetate phthalate, an ethyl vinyl phthalate, cellulosetriacetate, a polyanhydride, a polyglutamate, a polyhydroxy butyrate,polyvinyl acetate, a vinyl acetate-ethylene copolymer, a vinylacetate-vinylpyrrolidone copolymer, an acrylic polymer, an alkylacrylate polymer, an aryl acrylate polymer, an aryl methacrylatepolymer, a poly(caprolactam), an epoxy resin, a polyamine epoxy resin, apolyamide, a polyvinyl alcohol polymer, a polyalkyd resin, a phenolicresin, an abietic acid resin, a silicone, a polyalkylene oxide, and apolyester.
 47. The method of claim 19, wherein the hydrophobic solutionfurther comprises a plasticizer.
 48. The method of claim 19, wherein themean diameter of said particle is in the range of from about 0.1 micronsto about 200 microns.
 49. The method of claim 19, wherein the meandiameter of said particle is in the range of from about 0.2 microns toabout 100 microns.
 50. The method of claim 19, wherein the mean diameterof said particle is in the range of from about 0.5 microns to about 50microns.
 51. The method of claim 19, further comprising producing afungicidal composition by intermixing said particles with anagricultural adjuvant.
 52. The method of claim 51, wherein thefungicidal composition is in the form of a liquid suspension.
 53. Themethod of claim 51, wherein the fungicidal composition is in the form ofa wettable powder.
 54. The method of claim 51, wherein the fungicidalcomposition is in the form of a granule.
 55. The method of claim 54,wherein the granule is a water-dispersible granule.
 56. The method ofclaim 51, wherein the agricultural adjuvant comprises a dispersant. 57.The method of claim 51, wherein the agricultural adjuvant comprises adiluent.